Chemosensory transduction

CHEMOSENSORY TRANSDUCTION THE DETECTION OF ODORS, TASTES, AND OTHER CHEMOSTIMULI Edited by FRANK ZUFALL University of Saarland School of Medicine, Homburg, Germany STEVEN D MUNGER University of Florida, Gainesville, FL, USA AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, UK 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, USA The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK Copyright © 2016 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 978-0-12-801694-7 For information on all Academic Press publications visit our website at https://www.elsevier.com/ Typeset by TNQ Books and Journals www.tnq.co.in Cover Image: Original artwork by Dr Stephan Vigues showing a cartoon rendering of the canonical mammalian olfactory transduction cascade Contributors Barry W Ache Whitney Laboratory for Marine Bioscience, St Augustine, FL, USA; Departments of Biology and Neuroscience, Gainesville, FL, USA; Center for Smell and Taste, McKnight Brain Institute, University of Florida, Gainesville, FL, USA Sayoko Ihara Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, Japan Hubert Amrein Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, Bryan, TX, USA Sue C Kinnamon Department of Otolaryngology, University of Colorado Medical School, Aurora, CO, USA Sigrun Korsching Institute of Genetics, Biocenter, University at Cologne, Cologne, Germany Mari Aoki Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany Tsung-Han Kuo Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA Maik Behrens Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Trese Leinders-Zufall Department of Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany Ulrich Boehm Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany Qian Li Department of Cell Biology, Harvard Medical School, Boston, MA, USA Pablo Chamero Department of Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland School of Medicine, Homburg, Germany Stephen D Liberles Department of Cell Biology, Harvard Medical School, Boston, MA, USA Elizabeth A Corey Whitney Laboratory for Marine Bioscience, St Augustine, FL, USA; Center for Smell and Taste, McKnight Brain Institute, University of Florida, Gainesville, FL, USA Jeffrey R Martens Department of Pharmacology and Therapeutics, Center for Smell and Taste, University of Florida, College of Medicine, Gainesville, FL, USA Sami Damak Nestlé Research Center, Lausanne, Switzerland Jeremy C McIntyre Department of Pharmacology and Therapeutics, Center for Smell and Taste, University of Florida, College of Medicine, Gainesville, FL, USA Christopher H Ferguson Department of Biology, The Johns Hopkins University, Baltimore, MD, USA Wolfgang Meyerhof Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany Bill Hansson Department Evolutionary Neuroethology, Max Planck Institute for Chemical Ecology, Jena, Germany ix x CONTRIBUTORS Steven D Munger Center for Smell and Taste, University of Florida, Gainesville, FL, USA; Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA Yoshihito Niimura Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, Japan Yuzo Ninomiya Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan; Division of Sensory Physiology, Research and Development Center for Taste and Odor Sensing, Kyushu University, Fukuoka, Japan Gregory M Pask Department of Entomology, University of California Riverside, Riverside, CA, USA Nanduri R Prabhakar Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, Biological Sciences Division, University of Chicago, Chicago, IL, USA Anandasankar Ray Department of Entomology, University of California Riverside, Riverside, CA, USA; Institute for Integrative Genome Biology, University of California Riverside, Riverside, CA, USA Ivan Rodriguez Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland; Geneva Neuroscience Center, University of Geneva, Geneva, Switzerland Noriatsu Shigemura Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan Jay P Slack Department of Science and Technology, Givaudan, Cincinnati, OH, USA Marc Spehr Department of Chemosensation, Institute for Biology II, RWTH Aachen University, Aachen, Germany Lisa Stowers Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA Shingo Takai Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan Kazushige Touhara Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan; ERATO Touhara Chemosensory Signal Project, JST, The University of Tokyo, Tokyo, Japan Shuping Wen Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany Dieter Wicher Department Evolutionary Neuroethology, Max Planck Institute for Chemical Ecology, Jena, Germany Ryusuke Yoshida Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan Haiqing Zhao Department of Biology, The Johns Hopkins University, Baltimore, MD, USA Foreword remarkable collection What makes the chemical sense so intriguing as a subject for study is that almost all the mechanisms we know of for performing this transduction function are embodied in one or the other of the sensory systems devoted to sensing environmental chemicals Classically, we think of these as just smell and taste, but really there is much more diversity What we call the senses of smell and taste are in fact a collection of senses that work in many different ways Those different ways are the subjects of the chapters in this book A little bit of history Studies of olfactory and taste transduction were in many ways responsible for ushering in the modern era of chemical senses research Studies using the most sophisticated techniques from molecular biology and electrophysiology throughout the 1980s uncovered the first complex mechanisms of chemical transduction These studies were critical because they showed that the chemical senses worked like many other signaling systems in the brain and that they were not some idiosyncratic and strange island of neuroscience What we learned from other brain and sensory systems could be applied to olfaction and taste and vice versa We were in the mainstream of neuroscience All this led up to the landmark discovery of the mammalian odor receptors in 1991, the insect receptors in 1999, and the basic taste receptors in the early 2000s In a shockingly short period for science, the chemical senses went from a cul-de-sac of neuroscience to one of the most exciting frontiers of neuroscience And there it has Virtually everything that we know about the world comes to us through the little holes in our headdeyes, ears, nose, mouth Our brains sit protected inside a hard skull bathed in warm salty solutiondand completely in the dark, as they say It/we depend on our sensory organs to tell us about the world Inside each of those holes in our heads is a specialized piece of tissue that has evolved to be especially sensitive to a particular physical stimulusdelectromagnetic waves for vision, mechanical air pressure changes for sound, and chemicals of an immense variety for tastes and smells But most important, none of these physical stimuli themselvesdradiation, pressure, or environmental chemicalsdever reach the brain itself Only a signal that they are present is sent to the brain This process of changing a physical stimulus into a neural signal is the job of the specialized cells in the tissues of your sense organs It is a process we call transduction, and it is just this side of magic All the wonderful sensations connected with smells and tastesdfrom food to sex to the aesthetics of incense and the remarkably compelling memories of emotional moments in our livesdare first transduced by these hard-working little cellular machines Evolution has hit on numerous ways to get this to happen Most of them involve various sorts of proteins that work together in a carefully coordinated set of steps that transform a captured molecule into a small change in voltage that can be read by the brain All of this science will be treated in great detail and clarity in the chapters of this xi xii FOREWORD remained, as this volume will demonstrate to the reader In many ways, though, what is most remarkable to this old hand is how different a book on olfactory and taste transduction would have been a mere decade ago By my count, at least 10 of the chapters in this volume would not have even appeared a decade agodwe just did not know about many of these things And, of course, all the chapters have content not even imagined a decade past Will progress continue at this rate? Will this book be out of date soon? One hopes so I imagine a young reader, graduate student, or postdoctoral fellow being excited by this material, seeing in it endless opportunities, and setting out to make the next decade of unimagined discoveries I look forward to the next volume Stuart Firestein New York, 2015 Preface Chemical stimuli can inform us about the palatability, safety, and nutritional value of food; alert us to the presence of potential predators or other dangers; and guide our social interactions Animals of all types employ a variety of detection mechanisms that recognize these chemical cues present in the external or internal environment and convert that stimulus detection into neural or endocrine responses on which the organism can act Over the past 30 years, the details of this process, known as chemosensory transduction, have come into sharper focus; exploring these details and how they link us to our chemical world is the purpose of this book Each of us has a longstanding interest in understanding how the diversity of chemosensory transduction mechanisms enables both vertebrates and invertebrates to sense the complexity of the chemical world Our individual research programs (and our 15-plus years of collaboration) focus on the sensory transduction mechanisms that are critical for mammalian chemosensation However, we have each spent time studying olfaction in arthropods and retain a keen interest in differences and commonalities of smell and taste function across the animal kingdom When Melanie Tucker (Senior Acquisitions Editor at Academic Press/ Elsevier) first suggested to one of us (Zufall) that a book focused on olfaction might be a timely addition to the literature, we quickly recognized that what was lacking was an inclusive view of how odors, tastes, and other chemostimuli are recognized and encoded by the diverse array of chemosensory systems in a variety of animals Thus, we embarked on this 2-year effort, with the help of many of the leaders in chemosensory science, to produce the book you see here We hope that you, the reader, will find that it informs you about the complexity of chemosensation, guides you to the intricate and revealing scientific studies that we can only touch on here, and inspires you to investigate any of the many unanswered questions about how we sense our chemical world As with so many major undertakings, this book could not have been started (let alone published) without the invaluable contributions of many We would like to thank Melanie Tucker, Kristi Anderson, and the production and marketing staff at AP/ Elsevier for helping us to refine our ideas for this volume, recruit the many chapter authors, and navigate all the unfamiliar processes that are part of bringing a book to print Both were helpful and patient but not afraid to prod a bit when it was needed We thank Stephan Vigues, an accomplished chemosensory researcher in his own right with more than a little artistic talent, who created the cover art for the book This picture not only represents many of the molecules that can be found in a typical transduction cascade, but also conveys the activity of this living cellular machinery We are indebted to Stuart Firestein for providing an insightful and entertaining Foreword Stuart’s own research has been instrumental in illuminating the molecular and physiological mechanisms by which the xiii xiv PREFACE mammalian nose detects and encodes odors He has mentored, either formally or informally, many of the authors of this book as well as both of us More recently, he has been quite successfully and effectively engaging in the public communication of science We encourage you to read his fascinating insights on the importance of both Ignorance and Failure in his books by those names And of course, we heartily thank the many authors that contributed to this book Book chapters are often thankless work and may not seem to have the payoff of other activities, such as writing a review paper in a top journal But these friends and colleagues joined us in this endeavor anyway, and the book is all the better for it We hope that the participation, and the final product, has been rewarding for them In addition, we each have our own thanks to express Zufall: First and foremost, I would like to thank my academic mentors who guided my scientific journey from Germany to the United States and back: Randolf Menzel (Berlin); Hanns Hatt and Josef Dudel (Munich); Gordon Shepherd, Stuart Firestein, and Charles Greer (New Haven); and Michael Shipley (Baltimore) I’d like to express my gratitude to all present and former members of our laboratories who contributed to building a lasting research record in this field as well as the numerous individuals who teamed up with us on this exciting endeavor I am grateful to the Deutsche Forschungsgemeinschaft for funding much of my own research and for supporting the national research program “Integrative Analysis of Olfaction” for the past years Finally, I’d like to thank Trese LeindersZufall, my wife and long-term collaborator, and our daughter Nicola who have been a constant source of inspiration Munger: My coeditor Frank Zufall deserves special thanks As mentioned, Frank and I have been collaborators (and friends and colleagues) for more than 15 years, a relationship I hope will continue for many more I’d like to express my deep appreciation to the many other colleagues and mentors I have encountered over the nearly 30 years I have spent studying the chemical senses (many of which are chapter authors), including those who have worked with me in my laboratory Scientists in other disciplines may not appreciate the uniqueness of this community, including its strong support for its most junior members and enthusiastic appreciation of the power of fundamental science There are many reasons why I have continued to work in this field since I first discovered it while I did undergraduate research in Mike Mellon’s laboratory, but my colleagues are far from the least of them I’d like to thank the National Institute on Deafness and Other Communication Disorders, which funds much of the research in the chemical senses (including in my own laboratory) Without their diehard support of this field, we would know very little about these senses and how they impact our daily lives Finally, I would like to thank my very supportive family, especially my wife Caroline, son Garrett, and daughter Gwynn They are more tolerant than I deserve and more inspiring than they know Frank Zufall, PhD Homburg, Saarland, Germany Steven D Munger, PhD Gainesville, Florida, USA September 21, 2015 Introduction and Overview Frank Zufall, Steven D Munger signals for conspecific insects (but not for other insect species) is a dramatic example of how a compound can carry a very specific meaning based on the receiver’s ability to perceive it But no matter what information a chemical stimulus may convey, it is useless if it cannot be detected by a chemosensory organ and communicated to the nervous or endocrine systems to evoke a perception, behavior, or physiological change This process by which odors, tastes, and other chemical stimuli are detected and converted into a cellular signal is known as chemosensory transduction, and is the subject of this book The study of chemosensory transduction has seen an explosion of knowledge in recent years about the molecular biological, genetic, and physiological mechanisms that convert chemical information to cellular, neural, and endocrine responses, and has thus propelled this small field into the mainstream of membrane signaling and placed it at the forefront of elucidating the cellular and molecular logic of the nervous system Therefore, this book will not only explore the machinery of chemosensory transduction in both vertebrates and invertebrates but will highlight the organizational principles underlying the recognition of chemical stimuli Hay smells different to lovers and horses Stanislaw Jerzy Lec Animals rely on their chemical senses to make their way in the world The environment contains a complex mixture of chemicals that convey important, and sometimes critical, information that can influence what we eat, affect our interactions with others, help protect us from dangers, and impact our feelings and behaviors As is suggested in the quotation, the meaning of a chemical stimulus can vary based on our experience: although the smell of hay may trigger hunger in a horse, that same smell evokes a very different feeling for two young people seeking a place for a private rendezvous The aversive bitterness of beer or coffee may be off-putting with the first taste, but you can learn to appreciate it once it is paired with the pharmacological effects of alcohol or caffeine or the pleasure you feel when drinking these beverages in the company of friends In other words, context matters when it comes to the meaning of odors or tastes The neural circuitry that conveys and processes chemosensory information can also dictate its meaning Many animals have specialized chemosensory subsystems that mediate narrowly circumscribed behaviors that are essential to health, reproduction, survival, or even social relationships For example, although normal mice may cower when they smell TMT, a component of predator urine, mice that lack the most dorsal aspects of the olfactory system (that near the top of the head) can still smell the TMT, but no longer show signs of fear The ability of certain odor blends to act as attractive WHAT IS CHEMOSENSORY TRANSDUCTION? Chemosensory transduction may be defined as the process by which chemical stimulidincluding odors, tastes, nutrients, xv xvi INTRODUCTION AND OVERVIEW irritants, and even gasesdare detected and converted into internal signals that elicit changes in cellular membrane properties or the release of transmitters or hormones These processes usually take place within specialized cells, such as sensory neurons, that often contain dedicated subcellular compartments (such as cilia or microvilli) that are optimized for the transduction process In most cases, chemosensory transduction is a multistep mechanism in which biochemical membrane signals will be converted into electrical signalsdsuch as graded receptor potentials, action potential sequences, or bothda process that is known as chemoelectrical transduction We distinguish between primary signal transduction (e.g., the initial detection and transduction steps taking place within the ciliary structures of an olfactory sensory neuron) and subsequent processes within the same cell that further shape and modulate the output signal of a given sensory neuron As in sensory receptor cells from other modalities, a set of common operations can be defined in chemosensory cells that include the detection and discrimination of stimuli, amplification and sensory channel gating, adaptation, termination, and signal transmission to the brain In combination, these distinct mechanisms will enable a chemosensory cell to transduce an external molecular cue into an internal signal that can be encoded, propagated, and processed by the nervous system LEVELS OF ANALYSIS IN CHEMOSENSORY SYSTEMS The study of chemosensory transduction brings together people with diverse expertise: chemists, perfumers, and applied food scientists; geneticists and molecular biologists studying how the genome links to the unique chemosensory functions of an organism; neurobiologists and biophysicists interested in the function of the nervous system; psychophysicists that seek to understand how sensory stimuli influence behavior; behavioral endocrinologists and immunologists; and even clinicians interested in understanding the mechanistic basis of sensory disorders in humans and how to develop effective strategies for diagnosis and treatment Accordingly, modern studies of chemosensory transduction include, but extend far beyond, mechanistic analyses of stimulus detection in sensory cells The individual chapters of this book, which are written by chemosensory scientists at the forefront of their field, will provide evidence that a rich diversity of chemosensory systems have evolved in both vertebrates and invertebrates to sense chemical (i.e., molecular) information This diversity can even be found within a single chemosensory organ such as the mammalian olfactory epithelium (which resides in the nose) or gustatory epithelium (on the tongue and palate) An important development in the field has been the finding that the noncanonical expression of specific receptors outside the olfactory or gustatory systems is critical for sensing many internal chemostimuli, such as ingested nutrients and blood gases Therefore, the principles obtained from an analysis of the olfactory and taste systems can be applied equally well to understanding the mechanisms of internal chemosensing and homeostatic regulation within the body SECTION I: SOCIAL ODORS AND CHEMICAL ECOLOGY One important branch of modern chemosensory research aims at answering systems-level questions that are focused at understanding how the sensing of specific chemostimuli alters the behavioral response INDEX Caffeine, 383 Calcium homeostasis modulator (CALHM1), 276 CALHM1 See Calcium homeostasis modulator (CALHM1) Calmodulin (CaM), 128 CaM See Calmodulin (CaM) CaM-dependent protein kinase II (CaMKII), 129 CaMKII See CaM-dependent protein kinase II (CaMKII) cAMP See Cyclic adenosine monophosphate (cAMP) cAMP-responsive element (CRE), 58 Cannabinoid receptor (CB1), 305 Capillary Feeding Assay (CAFE Assay), 253 Capsaicin, 377e378 Carbon dioxide (CO2), 103, 322 carotid body sensory response, 330 in ventilatory response, 330 sensing and signaling pathways, 331f sensing by aortic bodies, 333 sensory transduction, 330e331 Carbon disulfide (CS2), 16e17 Carbon monoxide (CO), 142, 324e326 Carboxylic acids, 260 Carotid body See also Aortic bodies anatomical location and morphology, 322e323 blood flow and O2 consumption, 323 innervation, 323 sensory response to CO2, 330 tissue PO2, 323 in ventilatory response to CO2, 330 Carotid sinus nerve, 323 Catsup gene, 35 CB1 See Cannabinoid receptor (CB1) CBS See Cystathionine b-synthase (CBS) CCK See Cholecystokinin (CCK) CD36, 367 cDNA See complementary DNA (cDNA) Cell systems, expression in, 115 Centrosomal protein 290 (CEP290), 164 CEP290 See Centrosomal protein 290 (CEP290) Cephalochordates, 57 Cerambycid beetle (Megacyllene caryae), 106e107 Cerebrospinal fluid (CSF), 339e341 signaling molecules in, 342t CETN2 See Transgenic expression of centrin2 (CETN2) CFTR See Cystic fibrosis transmembrane conductance regulator (CFTR) cGKIa See cGMP kinase Ia (cGKIa) cGMP kinase Ia (cGKIa), 149e150 cGMP/cAMP-sensitive PDE1c, 148e149 Chaperones, 57e58 395 Chemesthesis, 376 chemesthetic agents, 377 compounds, sources, and TRP channel targets, 379te380t KCNK channels, 385e387 somatosensory response, 376 TRPM8, 378e381 TRPV1, 377e378 Chemical signaling, 38e39 Chemical signals, 31e32 Chemoreceptors, 184b Chemosensation, 6b, 29 Chemosensory ligands, 3e4, 10 Chemosensory organs, 4e5 Chemosignaling, 31 Chemosignals, 39e40 Chemostimuli, 31e32 Chinese hamster ovary cells (CHO cells), 115 Chlamydomonas reinhardtii (C reinhardtii), 162 CHO cells See Chinese hamster ovary cells (CHO cells) Cholecystokinin (CCK), 300, 305e306, 362 Chorda tympani (CT), 301e302 Chordates, 57 Choroid plexuses (CPs), 339e341 transport proteins, 342e343 Chrysanthemum plants, 41b Ciliary axoneme, 159e160 Ciliary compartment, 164 Ciliary trafficking of transduction molecules cilia structure, 159e161 mutations, 160f ciliary localization of odorant receptors, 165e166 ciliopathies and olfactory function, 167 ciliopathy-induced anosmia treatments, 169 lipid composition, 161e162 mechanisms regulating selective ciliary enrichment, 164e165 microvilli and chemical detection, 166b olfactory cilia-related genes, 167te168t protein movement within cilium, 162e164 Ciliated neuron, 93, 95 Ciliopathies, 157e158, 167 Ciliopathy-induced anosmia treatments, 169 Cilium, 159 protein movement within, 162e164 Circumvallate papillae (CV), 303e304 cis-vaccenyl acetate (cVA), 106e107 Citrus fruits, 38 Class I genes, 53 Class II genes, 53 Clawed frog (Xenopus laevis), 82, 90 396 CNG channels See Cyclic nucleotide-gated channels (CNG channels) CNGA2 See Cyclic nucleotide gated ion channel (CNGA2) CNGA4, 127e128 CNGB1b, 127e128 CNV See Copy number variation (CNV) CO2-sensitive gustatory receptors, 110 See also Ionotropic receptors; Odorant receptors manipulation detection in mosquitoes, 111e112 odor mixtures processing in insects, 112b receptor evolution and conservation, 110e111 structure/function, 111 CoA See Cortical amygdala (CoA) Coding lines, 184e185 Coelacanths, 89 Coelacanths (Latimeria), 82 Combinatorial coding, 15e16, 60 Comparative olfactory transduction functional subsets of OSNs, 209e210 gaining insight from, 216e218 LiSS by GPCRs, 215b noncanonical odorant-evoked signaling pathways, 212 noncompetitive mechanisms of inhibition, 214e216 olfactory receptors, 210e211 comparison with signal transduction mechanisms, 211f olfactory systems, 208 functional organization, 208e209 opponent signaling, 213e214 complementary DNA (cDNA), 127 complementary RNA (cRNA), 115 Copy number variation (CNV), 53 Cortical amygdala (CoA), 17 Corticotropin-releasing factor (CRF), 344 CP-CSF system, 343 in aging and neurological diseases, 343 and behavior, 344 CPs, 341e343 CSF, 341 in neurogenesis, 343 CPs See Choroid plexuses (CPs) CRD See Cysteine-rich domain (CRD) CRE See cAMP-responsive element (CRE) CRF See Corticotropin-releasing factor (CRF) cRNA See complementary RNA (cRNA) Crypt neurons, 95 CSE See Cystathionine-g-lyase (CSE) CSF See Cerebrospinal fluid (CSF) CT See Chorda tympani (CT) Cultured cells, 115 CV See Circumvallate papillae (CV) INDEX cVA See cis-vaccenyl acetate (cVA) Cyclic adenosine monophosphate (cAMP), 123, 141e142, 158e159, 276e277 axon targeting of olfactory sensory neurons, 125b changes, 124 future directions, 131e134 importance, 124e125 molecular identification of olfactory transduction components, 127e128 olfactory response dynamics, 132f in olfactory transduction, 125e127 OMP, 134b pathway, 94 regulation, 128 AC3, 129 Ca2+, 129 modulatory subunits, 130e131 olfactory transduction, 130 PDE1C, 129 PMCA, 131 receptor phosphorylation, 130 Ric-8b, 130 signaling, 141e142 cyclic nucleotide PDEs, 148e149 future perspectives, 149e150 mammalian olfactory, 143f membrane-bound guanylyl cyclase, 145e148 necklace system, 147b sGC, 142e145 techniques for monitoring changes, 149e150 synthesis and degradation, 124f vertebrate olfactory transduction, 126f Cyclic nucleotide gated ion channel (CNGA2), 70, 124, 158e159 Cnga2 null mutant mice, 7e9 Cyclic nucleotide phosphodiesterases (Cyclic nucleotide PDEs), 148e149 Cyclic nucleotide-gated channels (CNG channels), 61, 141e142, 158e159, 165, 210 Cyclohexylamine, 71e72 Cyclopentanone, 111 Cygnets, 149e150 Cystathionine b-synthase (CBS), 325 Cystathionine-g-lyase (CSE), 325 Cysteine-rich domain (CRD), 228 Cystic fibrosis transmembrane conductance regulator (CFTR), 58 D D-tubocurarine, 41b D-V axis See Dorsal-ventral axis (D-V axis) DA See Dopamine (DA) DAG See Diacylglycerol (DAG) INDEX Darcin See MUP20 Datura wrightii (D wrightii), 40 DCS See Diffuse chemosensory system (DCS) Dead horse arum (Helicodiceros muscivorus), 39e40 Deep sequencing analysis, DEET, 110 DEG See Degenerin (DEG) Degenerin (DEG), 288e289 Degenerin/epithelial Na channel protein family (Deg/ENaC protein family), 262 3,4-dehydro-exo-brevicomin (DHB), 13 Deorphanized receptors, 93e94 Desensitization, 61 DHB See 3,4-dehydro-exo-brevicomin (DHB) Diacylglycerol (DAG), 197e198, 276 Diamines, 76 DIDS See 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS) Diet induced obese (DIO), 301e302 Diffuse chemosensory system (DCS), 364b 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid (DIDS), 331 DIO See Diet induced obese (DIO) Diphenylborinic anhydride (DPBA), 385 Distributed gustatory system in insects, 248 DmOr67d receptor, 38 2-DMP, 16 DmXR, 260 Dopamine (DA), 329e330 Dorsal root ganglia (DRG), 377 Dorsal-ventral axis (D-V axis), 125b DPBA See Diphenylborinic anhydride (DPBA) DRG See Dorsal root ganglia (DRG) Drosophila melanogaster See Fruit fly (Drosophila melanogaster) Drosophila ORNs, expression in, 114 Drosophila sechellia (D sechellia), 35, 104 Drosophila taste neurons, 260e261 Dysosmia, 157e158 E E-11e14-acetate, 37e38 Ectopic expression of OR genes, 61e62 Electron microscopy, 323 Empty neuron system, 104, 106, 114 ENaC See Epithelial Na+ channel (ENaC) Enkephalins (ENK), 329e330 Enterocytes, 364 Enteroendocrine cells, 361e362 Epithelial Na+ channel (ENaC), 288e289, 304 mediating appetitive taste of sodium salts, 289f ERG channel See Ether-à-go-go-related channel (ERG channel) 397 ESP22 small peptide, 15, 182 ESPs See Exocrine gland-secreting peptides (ESPs) Ether-à-go-go-related channel (ERG channel), 196 Ethyl hexanoate, 35e36 European corn borer moth (Ostrinia nubilalis), 37e38 Excitation, 213e214 Exocrine gland-secreting peptides (ESPs), 10, 182 Exocytosis, 324 F Farnesyl pyrophosphate (FPP), 385 “Fat taste”, 238e239 Fatty acids, 260 receptors, 238e239 chain-length specificity, 238f FFAs See Free fatty acids (FFAs) Fish-like receptors, 85e86 Flavin monooxygenase (FMO3), 73e74 FlincGs, 150 Fluo4, 115 Fluorescence-resonance energy transfer (FRET), 149e150 FMO3 See Flavin monooxygenase (FMO3) Food, 375e376 odors, 33 Formyl peptide receptors (FPRs), 176, 182e183 See also Odorant receptors (ORs), Type vomeronasal receptors (V1Rs) functions, 183 genes, 182e183 Formyl-peptide receptors (FPRs), 10 Föster-resonance energy transfer See Fluorescenceresonance energy transfer (FRET) FPP See Farnesyl pyrophosphate (FPP) FPRs See Formyl peptide receptors (FPRs); Formyl-peptide receptors (FPRs) Free fatty acids (FFAs), 366 FRET See Fluorescence-resonance energy transfer (FRET) Fruit fly (Drosophila melanogaster), 31, 38, 103, 246 gustatory organs in, 247f Functional assay methods, 57e59, 58f Functional heterologous expression of taste receptors, 233b Fura-2, 115 G G protein, 58e59 G protein bg signaling (Gbg signaling), 276 pathway, 274f G protein-coupled receptor kinases (GRKs), 61 398 G proteinecoupled receptors (GPCRs), 7, 31e32, 50, 84, 107, 126e127, 163, 176e177, 193, 210, 212, 227e228, 271e272, 274e275, 326b, 360 LiSS by, 215b single heterodimeric, 255 G proteinecoupled taste receptors, 227e228 bitter taste receptors, 232e237, 232f deorphaned vertebrate, 235t gene repertoires, 234f structureefunction relationships, 236e237 fatty acid receptors, 238e239 chain-length specificity, 238f functional heterologous expression, 233b implication in orosensory detection of amino acids and peptides, 230f sweet taste receptor, 229e230 heteromer, 228f TAS1Rs, 228e229 TAS2R gene repertoires of vertebrates, 233e234 receptive ranges of, 235e236 umami taste receptor(s), 230e231 G proteinecoupled taste transduction ATP release and gustatory afferents activation, 280 confocal z-stack images of taste buds, 273f downstream signaling effectors, 275 G protein signaling regulation, 279 Ga signaling, 276e278 Gbg signaling, 276 G protein bg pathway, 274f GPCRs, 274e275 taste cell types and innervation, 272 GABAARs See Type A g-aminobutyric acid receptors (GABAARs) GAD67 See Glutamate decarboxylase (GAD67) GAL4/LEX alleles, 255 GAL4/UAS system, 253e254 Galanin, 309 Gaseous mediator molecules See Gaseous messengers Gaseous messengers, 142 Gastrointestinal tract (GI tract), 359 GC-D See Guanylyl cyclase D (GC-D) GC-G, 141e142, 145e146 GDP See Guanosine diphosphate (GDP) GEF See GTP exchange factor (GEF); Guanine nucleotide exchange factor (GEF) Gene knockout studies, 134b GFP See Green fluorescent protein (GFP) GG See Grueneberg ganglion (GG) Ghrelin, 308e309 Ghrelin receptor (GHSR), 308e309 Ghrelin-O-acyltransferase (GOAT), 308 GHSR See Ghrelin receptor (GHSR) INDEX GI tract See Gastrointestinal tract (GI tract) GIP See Glucose-dependent insulinotropic polypeptide (GIP) GIRK1 channel, 196 Glomerulus, 102e103 Glomus cells See Type I cells GLP-1 receptor (GLP-1R), 300 GLP-1 See Glucagon-like peptide-1 (GLP-1) GLP-1R See GLP-1 receptor (GLP-1R) Glucagon, 303 Glucagon receptor (GlucR), 303 Glucagon-like peptide-1 (GLP-1), 300, 303e304, 362 Glucose sensitivity for energy expenditure regulation, 347 Glucose transporter (GLUT), 347 GLUT2, 364e366 Glucose-dependent insulinotropic polypeptide (GIP), 362 GlucR See Glucagon receptor (GlucR) GLUT See Glucose transporter (GLUT) Glutamate, checkpoint for, 347e348 Glutamate decarboxylase (GAD67), 300 Gnai, Gnao, GnRH See Gonadotropin-releasing hormone (GnRH) GOAT See Ghrelin-O-acyltransferase (GOAT) Gonadotropin-releasing hormone (GnRH), 344, 349f GPCR kinase (GRK3), 61, 130 GPCRs See G proteinecoupled receptors (GPCRs) GPR120, 366 GPR40 expression, 366e367 GPR92, 368 Gr family See Gustatory receptor family (Gr family) Gr genes See Gustatory receptor genes (Gr genes) Green fluorescent protein (GFP), 161, 276 GRK3 See GPCR kinase (GRK3) GRKs See G protein-coupled receptor kinases (GRKs) GRNs See Gustatory receptor neurons (GRNs) GRs See Gustatory receptors (GRs) Grueneberg ganglion (GG), 145e146, 147b Grueneberg ganglion, 68 GTP See Guanosine triphosphate (GTP) GTP exchange factor (GEF), 130 GTPase See Guanosine triphosphatase (GTPase) Guanine nucleotide exchange factor (GEF), 57e58, 279 Guanosine diphosphate (GDP), 274 Guanosine triphosphatase (GTPase), 274 Guanosine triphosphate (GTP), 142, 274 Guanylate cyclase (gucy2f), 94 Guanylyl cyclase D (GC-D), 16e17, 141e142, 145e146 Gucy1b2, 94, 142e144 INDEX gucy2f See Guanylate cyclase (gucy2f) Gustatory afferents activation, 280 Gustatory function behavioral analysis, 251 behavioral assays for measuring taste responses, 252f CAFE Assay, 253 oviposition assay, 253 proboscis extension assay, 251e252 two-choice feeding assay, 252e253 cellular analysis, 250 Ca2+ imaging, 251 tip recordings, 250e251 Gustatory nerve, 300e304 Gustatory organs in D melanogaster, 247f Gustatory perception in larvae, 262 larval gustatory system, 263f Gustatory receptor family (Gr family), 110 Gustatory receptor genes (Gr genes), 248e249, 253e254 noncanonical expression, 264e265 in olfactory system, 264 proteins as brain nutrient sensors, 264 beyond taste, 262e264 Gustatory receptor neurons (GRNs), 248e250, 255 Gustatory receptors (GRs), 31e32 Gustatory system, 288 Gut nutrient sensing amino acids, 367e368 DCS, 364b gut sense nutrients, 361 microbiota, 369 molecular sensors for carbohydrates, lipids, and proteins, 360t sensing carbohydrates, 364e366 sensing fat, 366e367 sensing proteins, 367e368 sensors location, 362e364 taste receptors, 360e361 taste signaling molecules in gut, 361 Trpm5-GFP transgenic mouse jejunum, 363f Gut sense nutrients, 361 Gaegustducin (Gagust), 276e277, 278f Gaq-type G protein, 57e58 Gbg signaling See G protein bg signaling (Gbg signaling) H Haplorhines, 55 Hawkmoth (Manduca sexta), 40 HCA See Hydroxycinnamic acid (HCA) 399 HCN channel family See Hyperpolarization-activated cyclic nucleotide-gated channel family (HCN channel family) HEK cells See Human embryonic kidney cells (HEK cells) HEK-293 cells, 71 HEK293 cells See Human embryonic kidney 293 cells (HEK293 cells) HEK293T cells, 59e60 Helicodiceros muscivorus See Dead horse arum (Helicodiceros muscivorus) Heme oxygenase-2 (HO-2), 325e326 2-heptanone, 16 Heterologous expression system, 59 HFD See High-fat diet (HFD) High-fat diet (HFD), 350 High-performance liquid chromatography (HPLC), 73 HMH See 6-hydroxy-6-methyl-3-heptanone (HMH) HO-2 See Heme oxygenase-2 (HO-2) Homologous expression system, 51e52 Homoserine lactones (HSLs), 279b HPLC See High-performance liquid chromatography (HPLC) HSLs See Homoserine lactones (HSLs) HTR6 See Serotonin receptor (HTR6) Human embryonic kidney 293 cells (HEK293 cells), 377 Human embryonic kidney cells (HEK cells), 115 Human(s), 375e376 bitter taste receptors, 237f OR genes in, 53e55 pheromones, 6b umami receptor, 229e230 Hydrogen cyanide, 53 Hydrogen sulfide (H2S), 325 cellular targets, 329f CSE-dependent H2S generation, 325e326 mediating sensory excitation, 325 Hydronium ion (HCO3 +), 292e294 6-hydroxy-6-methyl-3-heptanone (HMH), 13 Hydroxycinnamic acid (HCA), 34e35 Hypercapnia, 322, 330, 333 Hyperpolarization-activated cyclic nucleotide-gated channel family (HCN channel family), 196 HCN1, 294 Hypothalamus, 19 Hypoxanthine-3(N)-oxide, 92e93 Hypoxia, sensing by aortic bodies, 332e333 cellular basis of gas messengeremediated carotid body hypoxic sensing, 326e327 membrane hypothesis, 327e328 400 Hypoxia, sensing (Continued ) metabolic hypothesis, 328 O2 sensing signaling pathways, 327f excitatory neurotransmitter, 328e329 H2S mediating sensory excitation, 325 heme-oxygenase-2ederived CO, 325e326 interactions between neurotransmitters, 329e330 reflex response to hypoxia, 323e324 sensing variable, 324 sensory complex and sensory transduction site, 324 transduction machineries, 326b transduction mechanism, 325 I IA See Incensole acetate (IA) IFT See Intraflagellar transport (IFT) IGFs See Insulin-like growth factors (IGFs) iGluR See ionotropic glutamate receptor (iGluR) Immunohistochemical study, 94 Immunohistochemistry experiments, 70 Impaired olfactory function, 157e158 In silico screening, 115 In situ hybridization, 94 Incensole acetate (IA), 385 indels See Insertion-deletions (indels) Inhibition, 213e214 noncompetitive mechanisms, 214e216 of odorants, 158e159 Innate avoidance responses, 73 Insect homeostasis, 33 blood-feeding mosquitos, 35 D melanogaster, 33e34 D sechellia, 35 drosophilid flies of geosmin signal, 34f ethyl hexanoate, 35e36 odor signals, 36f ROSs, 34e35 Scaptomyza, 36e37 Insect olfactory receptors, 103 CO2-sensitive gustatory receptors, 110 manipulation detection in mosquitoes, 111e112 odor mixtures processing in insects, 112b receptor evolution and conservation, 110e111 structure/function, 111 insect olfactory sensillum and olfactory receptor families, 102f ionotropic receptors, 108 evolution, 108 functional characterization, 108e109 Ir-mediated behavior, 110 structure and function, 109 methods for functional characterization of, 105f activity imaging in vivo from neurons, 114 INDEX expression in cell systems, 115 expression in Drosophila ORNs, 114 in silico screening, 115 odorant receptors, 103 evolution, 103e104 ligands, 104e106 Or-mediated behaviors, 106 Or-mediated detection of pheromones, 106e107 structure/function, 107e108 odorants, 102e103 olfactory proteins at periphery, 113e114 primary olfactory appendages, 102 semiochemicals, 102 Insect(s), 246e247 distributed gustatory system, 248 olfaction, 112b reproduction, 37e38 taste cells, 248 Insecteplant interactions, 38e39 chemosignals, 39e40 D wrightii, 40 reaction chain, 39f Insects, chemical ecology in chemosensation, 29 chemosignaling, 31 chemostimuli and receptors, 31e32 evolutionary aspects, 40e42 hierarchical scheme of chemosignals, 31f insect homeostasis, 33 blood-feeding mosquitos, 35 D melanogaster, 33e34 D sechellia, 35 drosophilid flies of geosmin signal, 34f ethyl hexanoate, 35e36 odor signals, 36f ROSs, 34e35 Scaptomyza, 36e37 insect reproduction, 37e38 insecteplant interactions, 38e39 chemosignals, 39e40 D wrightii, 40 reaction chain, 39f odor classes, 32t pheromones, 30e31 plant products affecting ion channels in animals, 41b semiochemicals, 30, 30f Insertion-deletions (indels), 53 Insulin, 304 Insulin-like growth factors (IGFs), 341 Intraflagellar transport (IFT), 162, 169 Ion channels mediating secondary signaling events, 196 ionotropic glutamate receptor (iGluR), 108 INDEX Ionotropic receptors (IRs), 31e32, 41b, 103, 108 See also CO2-sensitive gustatory receptors; Odorant receptors evolution, 108 functional characterization, 108e109 genes, 254b Ir-mediated behavior, 110 structure and function, 109 IP3 See 1,4,5-trisphosphate (IP3) IP3R3 See Type IP3 receptor (IP3R3) Ir-mediated behavior, 110 Ir64a, 110 Ir84a, 110 Iron transporter, 348 IRs See Ionotropic receptors (IRs) Isoamylamine See Isopentylamine Isopentylamine, 71e72 J Jacobson organ, 176 K K+ channels See Potassium ion channels (K+ channels) Kairomones, 4, 13e15, 30 Kappe neurons, 95 KCNK See Potassium channel subfamily K channels (KCNK) Kinesin family member 17 (KIF17), 162e163 knockdown resistance (kdr), 41b Knockout (KO), 364e366 L LA See Leptin receptor antagonist (LA) Labeled line hypothesis, 248e249 Lamprey migratory pheromone, 92 OR genes, 84 Lancet group, 126e127 Land-to-water transition, 91 Larval amphibians, 90 Leber congenital amaurosis (LCA), 167 LepRb receptor See Ob-Rb receptor Leptin, 301e302 Leptin receptor antagonist (LA), 301e302 Leptopilina boulardi (L boulardi), 38 Ligand-induced selective signaling (LiSS), 214e215 by GPCRs, 215b mechanism by mammalian OR, 217f LINEs See Long interspersed nuclear elements (LINEs) Lipid-soluble toxins, 41b LiSS See Ligand-induced selective signaling (LiSS) 401 LNs See Local interneurons (LNs) Lobe-finned fish, olfactory receptor gene repertoires of, 89 Local interneurons (LNs), 112b Long interspersed nuclear elements (LINEs), 177e178 LUSH protein, 113 M Macronutrient, 359e360 MadineDarby Canine Kidney cells, 161 Main olfactory bulb (MOB), 7e9, 70, 179, 209 Main olfactory epithelium (MOE), 4e5, 68, 90, 124e125, 142e144, 158e159, 166b, 208 detecting specialized ligands, 15e17 Major histocompatibility complex (MHC), 9, 92, 181e182 Major urinary proteins (MUPs), 10e13, 182, 196e197 Mammal, 288e289 Mammalian OR genes, 53 Mammalian-like receptors, 85e86 Mammals, 208e210 OR genes in, 55e56 Maxillary palps, 102 MeA See Medial amygdala (MeA) Medial amygdala (MeA), 17e19 Megacyllene caryae See Cerambycid beetle (Megacyllene caryae) Melatonin, 344 Membrane hypothesis, 326e328 Membrane-bound guanylyl cyclase, 145e148 Menthol, 377, 380e381, 385 Metabolic hypothesis, 326e328 metabotropic glutamate receptor (mGluR), 180, 360 metabotropic glutamate receptor-subunit 1a (mGluR1a), 348 Methyl hexanoate, 35e36 2-methylbutylamine, 71e72 (methylthio)methanethiol (MTMT), 59e60 mGluR See metabotropic glutamate receptor (mGluR) mGluR1a See metabotropic glutamate receptorsubunit 1a (mGluR1a) MHC See Major histocompatibility complex (MHC) Microbiota, 369 Microvillous neuron, 90, 93e94 Middle cavity, 90 Mitochondrial hypothesis See Metabolic hypothesis MKS3 See Transmembrane protein 67 (TMEM67) MOB See Main olfactory bulb (MOB) MOE See Main olfactory epithelium (MOE) Molecular basis of taste modalities, 253e260 amino acids, fatty acids, carboxylic acids, 260 bitter taste, 257e259 402 INDEX Molecular basis of taste modalities (Continued ) molecular diversity of Drosophila taste receptors, 254b salt taste, 259e260 sugar taste, 255 expression code for sugar receptors, 256f expression of Ir76b in labial and tarsal GRNs, 258f taste receptor genes with known function, 257t water taste, 259 Molecular diversity of Drosophila taste receptors, 254b Molecular genetics, Molecular profiling, 16 Molecular receptive range (MRR), 217e218 Monosodium glutamate (MSG), 360 mOR-EG, 59 MOR174e9 See mOR-EG MOR215e1, 60 MOR23, 52 MOR244e3, 59e60 MOR83 See MOR244e3 Morinda citrifolia See Noni fruit (Morinda citrifolia) Morinda citrifolia (M citrifolia), 35 Mosquito, manipulation detection in, 111e112 Most recent common ancestor (MRCA), 84 MRCA See Most recent common ancestor (MRCA) MRR See Molecular receptive range (MRR) MSG See Monosodium glutamate (MSG) MTMT See (methylthio)methanethiol (MTMT) Multigene family, 50, 56 MUP20, 14e15 MUPs See Major urinary proteins (MUPs) Mus caroli (M caroli), 73e74 Mus musculus (M musculus), 73e74 N N, N-dimethylcyclohexylamine, 76 N-arachidonoylethanolamine (AEA), 312b N-methylpiperidine, 76 Na+ channels See Sodium ion channels (Na+ channels) Na+ taste, amiloride-sensitive, 288 DEG/ENaC channel family, 289 primary Na+ taste sensor, 290 TRC subtype, 290 Na+-Ca2+ exchanger (NCKX4), 128 Na+/glucose cotransporter (SGLT-1), 364e366 nAChR See Nicotinic acetylcholine receptor (nAChR) NAD See Nicotinamide adenine dinucleotide (NAD) NCAM See Neural cell adhesion molecule (NCAM) NCKX4 See Na+-Ca2+ exchanger (NCKX4) Necklace system, 147b Nephronophthisis (NPHP4), 161 Neural cell adhesion molecule (NCAM), 300 Neuropeptide Y (NPY), 300, 306e307 Neurotransmitter excitatory, 328e329 interactions between, 329e330 New World monkeys (NWMs), 55 Niche for adult neurogenesis, 350 Nicotinamide adenine dinucleotide (NAD), 323 Nicotine, 41b Nicotinic acetylcholine receptor (nAChR), 41b Nitric oxide (NO), 142, 348e350 receptor, 94 Nitric oxide synthase (NOS), 82, 348e350 NO See Nitric oxide (NO) Noncanonical odorant-evoked signaling pathways, 212 Noni fruit (Morinda citrifolia), 37f Nonmammalian vertebrates, OR genes in, 57 NOS See Nitric oxide synthase (NOS) Nostrils, 55 NPHP4 See Nephronophthisis (NPHP4) NPY See Neuropeptide Y (NPY) Nutrient sensing, 367 NWMs See New World monkeys (NWMs) O Oak Ridge Polycystic Kidney mouse model (ORPK mouse model), 169 Ob-Rb receptor, 301e302 OBPs See Odorant-binding proteins (OBPs) ODEs See Odorant-degrading enzymes (ODEs) Odor, 92 discrimination mechanisms, 60 mixtures processing in insects, 112b recognition theory, 49e50 Odor-evoked inhibition, 214 Odorant receptors (ORs), 7, 31e32, 50e51, 67, 82, 103, 126e127, 158e159, 176e177, 183e184, 210e211 See also CO2-sensitive gustatory receptors; Formyl peptide receptors (FPRs); Ionotropic receptors; Type vomeronasal receptors (V1Rs) adenovirus approach, 52 canonical, 210 ciliary localization, 165e166 evolution, 103e104 functional aspect desensitization, 61 ectopic expression of OR genes, 61e62 functional assay methods, 57e59, 58f odor discrimination mechanisms, 60 physiological ligand pair, 59e60 structure and function, 59 INDEX genes in mammals, 55e56 in nonmammalian vertebrates, 57 in primates, 55 homologous expression system, 51e52 in humans, 53e55 ligands, 104e106 mammalian, 217f Or-mediated behaviors, 106 Or-mediated detection of pheromones, 106e107 phylogeny and numbers, 54f structure/function, 107e108 transmembrane structure, 51f Odorant-binding proteins (OBPs), 102e103, 113, 249e250 Odorant-degrading enzymes (ODEs), 113 Odorants, 60, 102e103 OEA See Oleoylethanolamide (OEA) Old World monkeys (OWMs), 55 Oleoylethanolamide (OEA), 364 Olfaction, 35, 208 Olfactory cilia-related genes, 167te168t dysfunction, 157e158 function, 167 G proteins, 164 information, 57 organs, 91 perception, 53, 208 proteins at periphery, 113e114 response dynamics, 132f sensilla, 102 sensory neuron types, 95 signaling proteins, 163e164 mechanisms regulating selective ciliary enrichment, 164e165 system, 67e68, 157e158, 208 functional organization, 208e209 TAARs, 70 transduction, 208e209 transduction cAMP in, 125e127 molecular identification, 127e128 Olfactory ligands, candidate specialized, 11te12t chemosensory ligands, 10 mouse VNO, 13e14 MUPs, 10e13 subtractive gas chromatography-mass spectrometry methods, 13 sulfated estrogen, 13 sulfated steroids, 13 403 VNO, 9e10 VNO-stimulating ligand families, 10 Olfactory marker protein (OMP), 95, 134b Olfactory neurons See Drosophila taste neurons Olfactory receptor neurons (ORNs), 102e103 Olfactory receptors (ORs), 82, 210e211, 255 comparison with signal transduction mechanisms, 211f gene loci, 53 repertoires, 55 Olfactory sensory neurons (OSNs), 31e32, 68, 82, 124e125, 141e142, 144, 158e159, 158f, 179, 199, 208, 218 arthropods, 209 “bursting”, 218 functional subsets of, 209e210 GC-D-expressing, 146 hypothetical, 213f OlfCa1, 87 OlfCc1, 87e88 Olfr gene, 70 Olfr1509 See MOR244e3 Olfr73 See mOR-EG OMP See Olfactory marker protein (OMP) “One receptor-one neuron” rule, 70 One zebrafish TAAR, 86 Ophrys apifera See Bee orchid (Ophrys apifera) Opponent signaling, 213e214 Or coreceptor (Orco), 103e104 Or-mediated behaviors, 106 Or-mediated detection of pheromones, 106e107 OR1D2, 62 Or22a receptor, 35e36 OR51E2, 62 Or67d-mutant flies, 106e107 Or71a, 34e35 Or94b larval-specific receptor, 34e35 ORA1, 93 Oral cavity, 360 Orco See Or coreceptor (Orco) Orco-mutant Aedes aegypti, 106 Orexigenic control by hormones, 347 Organ, 191 Organon vomeronasale See Vomeronasal organ (VNO) ORNs See Olfactory receptor neurons (ORNs) ORPK mouse model See Oak Ridge Polycystic Kidney mouse model (ORPK mouse model) ORs See Odorant receptors (ORs); Olfactory receptors (ORs) OSNs See Olfactory sensory neurons (OSNs) 404 Ostrinia nubilalis See European corn borer moth (Ostrinia nubilalis) Oviposition assay, 253 OWMs See Old World monkeys (OWMs) OXTR See Oxytocin receptor (OXTR) Oxygen (O2), 322 blood flow and O2 consumption, 323 sensing signaling pathways, 327f tension, 324 Oxytocin, 307e308 Oxytocin receptor (OXTR), 308 P PAIN See Painless (PAIN) Painless (PAIN), 259 Partial pressure of O2 (PO2), 323 Particulate guanylyl cyclases (pGC), 141e142 Pb1B neurons, 34e35 PC See Piriform cortex (PC) PC1/3 See Prohormone convertase 1/3 (PC1/3) PC2 See Prohormone convertase (PC2) PCR See Polymerase chain reaction (PCR) PDE1C, 129 PDEs See Phosphodiesterases (PDEs) PEPT1 See Peptide transporter (PEPT1) Peptide transporter (PEPT1), 368 Peptide tyrosineetyrosine (PYY), 300, 307, 362 PER index See Proboscis extension response index (PER index) pGC See Particulate guanylyl cyclases (pGC) 2-phenylethylamine, 72e73 Pheromones, 4, 30e31, 37, 176 Or-mediated detection of, 106e107 Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), 216 Phosphodiesterases (PDEs), 124, 141e142, 146e147, 276e277 Phosphoinositide 3-kinase (PI3K), 216 Phospholipase C (PLC), 94 Phospholipase C b2 (PLCb2), 276 Phylogenetic analyses, 103e104 Physiological ligand pair, 59e60 PI3K See Phosphoinositide 3-kinase (PI3K) Pickpocket gene (ppt gene), 254b PIP2 See 4,5-bisphosphate (PIP2) PIP3 See Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) Piriform cortex (PC), 17 PKA See Protein kinase A (PKA) PKC See Protein kinase C (PKC) PKD1L3 See Polycystic kidney disease 1-like (PKD1L3) PKD2L1 See Polycystic kidney disease 1-like (PKD2L1) INDEX PKG See Protein kinase G (PKG) Plant metabolism, 38e39 Plasma membrane Ca2+-ATPase (PMCA), 131 PLC See Phospholipase C (PLC) PLCb See b isoforms of phospholipase C (PLCb) PLCb2 See Phospholipase C b2 (PLCb2) PMCA See Plasma membrane Ca2+-ATPase (PMCA) PNs See Projection neurons (PNs) Polycystic kidney disease 1-like (PKD2L1), 300 Polycystic kidney disease 1-like (PKD1L3), 300 Polymerase chain reaction (PCR), 50, 127 Potassium channel subfamily K channels (KCNK), 385e387 chemesthetic agents in Szechuan pepper, 387f KCNK3, 294, 386e387 KCNK9, 386e387 KCNK18, 386e387 Potassium ion channels (K+ channels), 272 ppt gene See Pickpocket gene (ppt gene) Predator odor, 73 Primary olfactory appendages, 102 Primary signal transduction pathway(s), 196e199 Primates, OR genes in, 55 Primers, 30e31 Principal cavity of adult frogs, 90 Proboscis extension assay, 251e252 Proboscis extension response index (PER index), 251e252 Prohormone convertase 1/3 (PC1/3), 303 Prohormone convertase (PC2), 303 Projection neurons (PNs), 102e103, 112b Prostaglandins, 92 Prostate-specific GPCR (PSGR), 62 Protein kinase A (PKA), 61, 124, 125b, 130, 277 Protein kinase C (PKC), 61, 130 Protein kinase G (PKG), 325e326 Proteineprotein interactions, 164e165 Proton (H+), 292e294 PSGR See Prostate-specific GPCR (PSGR) Puncturing theory, 50 Pungency, 377, 385e386 Putative OR genes, 50e51 Pyrethrins, 41b PYY See Peptide tyrosineetyrosine (PYY) R Radiational theory, 50 Ray-finned fish, OR gene family of, 85e86 Reactive oxygen species (ROSs), 34e35 Receptor guanylyl cyclases See Particulate guanylyl cyclases (pGC) Receptor transporter protein (RTP1), 57e58 Receptor-dependent transduction pathways, 195e199 INDEX Reflex regulation by aortic bodies, 332 Regulators of G protein signaling (RGS), 279 RGS2, 129 Releasers, 30e31 Reproduction, 348 IGF-1, 350 NO, 348e350 RGS See Regulators of G protein signaling (RGS) Rhinarium, 55 Rhodopsin-like GPCR family, 50e51 Ric-8b, 130 RNA splicing, 68 Rodent TAARs, 86 ROSs See Reactive oxygen species (ROSs) RTP1 See Receptor transporter protein (RTP1) S Salt taste, 259e260 Sanshools, 385e386 Sarco-/endoplasmic reticulum Ca2+-ATPases (SERCA), 276 SBT See 2-sec-butyl-4,5-dihydrothiazole (SBT) Scaptomyza, 36e37 SCCs See Solitary chemosensory cells (SCCs) SCFAs See Short chain fatty acids (SCFAs) SD rats See SpragueeDawley rats (SD rats) 2-sec-butyl-4,5-dihydrothiazole (SBT), 13 Secondary signaling processes, 195e199 Semaphorin7A (Sema7A), 350 Semiaquatic species, 91 Semiochemicals, 4, 30, 102, 176 Sense of taste, 227e228 Sensilla, 208e209 Sensing carbohydrates, 364e366 fat, 366e367 proteins, 367e368 variable, 324 Sensors location, 362e364 Sensory complex and sensory transduction site, 324 Sensory neuron membrane proteins (SNMPs), 113 Sensory organs, 322 Sequence motifs, 165 SERCA See Sarco-/endoplasmic reticulum Ca2+-ATPases (SERCA) Serotonin receptor (HTR6), 165 Seven-transmembrane domain (7-TMD), 50e51, 51f, 228 Sex pheromones, 37 SEZ See Subesophageal zone (SEZ) sGC See Soluble guanylyl cyclase (sGC) SGLT-1 See Na+/glucose cotransporter (SGLT-1) 405 SH rats See Spontaneously hypertensive rats (SH rats) Short chain fatty acids (SCFAs), 367 Signal transduction mechanisms in vomeronasal signaling, 194f primary signal transduction pathway(s), 196e199 Signal transduction, 94 Single-nucleotide polymorphisms (SNPs), 53 Small ubiquitin-like protein (SUMO), 165 SNAP25 See Synaptosomal-associated protein (SNAP25) SNARE proteins, 280 SNMPs See Sensory neuron membrane proteins (SNMPs) SNPs See Single-nucleotide polymorphisms (SNPs) Social behavior, 10 transforming specialized ligands into, 19 Sodium chloride (NaCl), 304 Sodium ion channels (Na+ channels), 272 Solitary chemosensory cells (SCCs), 279b Soluble guanylyl cyclase (sGC), 141e145 Somatostatin receptor (SSTR3), 165 Sour taste, 291e292 channel and transporter types, 294 hydronium ion, 292e294 model for activation, 293f Specialized chemosignaling MOE detecting specialized ligands, 15e17 olfactory ligands, candidate specialized, 11te12t chemosensory ligands, 10 mouse VNO, 13e14 MUPs, 10e13 subtractive gas chromatography-mass spectrometry methods, 13 sulfated estrogen, 13 sulfated steroids, 13 VNO, 9e10 VNO-stimulating ligand families, 10 specialized odors, 3e4 specialized olfactory behavior, chemosensory organs, 4e5 Cnga2 null mutant mice, 7e9 deep sequencing analysis, human pheromones, 6b ligand-detecting GPCRs, molecular genetics, molecular identity of sensory neurons, 8f VNO receptors, 5e6, transforming specialized ligands into social behavior, 19 406 Specialized ligands MOE detecting, 15e17 neural circuits, 17 anatomical and functional division of VNO-activated circuits, 18f CoA, 17 hypothalamus, 19 VNO signaling, 19 VSN, 17e19 transforming into social behavior, 19 Specialized odors, 3e4 Specialized olfactory behavior, chemosensory organs, 4e5 Cnga2 null mutant mice, 7e9 deep sequencing analysis, human pheromones, 6b ligand-detecting GPCRs, molecular genetics, molecular identity of sensory neurons, 8f VNO receptors, 5e6, Spontaneously hypertensive rats (SH rats), 325 SpragueeDawley rats (SD rats), 325 SSTR3 See Somatostatin receptor (SSTR3) “Standard” Hodgkin-Huxley type voltage-activated conductances, 196 Steroids, 92 Strepsirrhines, 55 Structure-activity analysis, 76 Subarachnoid space, 339e340, 344 Subesophageal zone (SEZ), 250 Subtractive gas chromatography-mass spectrometry methods, 13 Sugar taste, 255 expression code for sugar receptors, 256f expression of Ir76b in labial and tarsal GRNs, 258f taste receptor genes with known function, 257t Sulcatone (6-methyl-5-hepten-2-one), 35 Sulfated steroids, 13 SUMO See Small ubiquitin-like protein (SUMO) SUMOylation, 165 Sustentacular cells See Type II cells Sweet proteins, 292b Sweet taste, 360e361 Sweet taste receptor, 229e230 See also Bitter taste receptors heteromer, 228f Sweet taste receptor heteromer, 228f Sweet taste reciprocal modulation, 312b Sweet-tasting substances, 292b Synaptosomal-associated protein (SNAP25), 300 Synomones, 30 INDEX T T1Rs See Type taste receptors (TAS1Rs) TAAR See Transient amino acid receptor (TAAR) TAARs See Trace amine-associated receptors (TAARs) Table salt (NaCl), 288 Tanycytes classification, 345e346 functional roles, 346 checkpoint for glutamate, 347e348 glucose sensitivity for energy expenditure regulation, 347 iron transporter, 348 niche for adult neurogenesis, 350 orexigenic control by hormones, 347 reproduction, 348e350 GLAST:CreERT2, 346f morphology, 344e345 rapid golgi section, adult rat, 345f Tas1r genes, 228 TAS1R1 receptor, 364e366 TAS1R1:TAS1R3, 368 heteromer, 230e231 receptors, 275 TAS1Rs See Type taste receptors (TAS1Rs) TAS2Rs See Type taste receptors (TAS2Rs) TASK See TWIK-related acid-sensitive K+ (TASK) TASK-1 See Potassium channel, subfamily K, member (KCNK3) Taste, 300 buds, 271e272 cells, 300, 301t receptors, 359e361 genes with known function, 257t signaling, 279b sensitivity, 301e302, 304, 306 signal transduction, 260e262 signaling molecules in gut, 361 Taste perception mechanism in Drosophila, 246 adult insect gustatory system, 246e250 distributed gustatory system in insects, 248 gustatory organs in D melanogaster, 247f organization of taste sensilla, 248e250, 249f SEZ, 250 behavioral analysis of gustatory function, 251 behavioral assays for measuring taste responses, 252f CAFE assay, 253 oviposition assay, 253 proboscis extension assay, 251e252 two-choice feeding assay, 252e253 cellular analysis of gustatory function, 250 INDEX Ca2+ Imaging, 251 tip recordings, 250e251 gustatory perception in larvae, 262 larval gustatory system, 263f gustatory receptors beyond taste, 262e264 Gr genes in olfactory system, 264 Gr proteins as brain nutrient sensors, 264 noncanonical expression of Gr genes, 264e265 molecular basis of taste modalities, 253e260 amino acids, fatty acids, carboxylic acids, 260 bitter taste, 257e259 molecular diversity of Drosophila taste receptors, 254b salt taste, 259e260 sugar taste, 255 water taste, 259 taste receptor types in adult flies, 261f taste signal transduction, 260e262 Taste receptor cells (TRCs), 288e289 Taste sensilla, organization of, 248e250, 249f Taste transduction, peptide signaling in, 310f, 311t See also G proteinecoupled taste transduction AngII, 304e305 CCK, 305e306 galanin, 309 ghrelin, 308e309 GLP-1, 303e304 glucagon, 303 insulin, 304 leptin, 301e302 NPY, 306e307 oxytocin, 307e308 peptide tyrosineetyrosine, 307 taste bud cells, 300, 301t VIP, 306 Teleost bile acid detection, 92 Teleost fish olfactory receptor gene repertoires, evolutionary dynamics of, 85e88 high evolutionary dynamics, 86 OR gene family of ray-finned fish, 85e86 T1R and T2R, 88b V1R-related Ora gene family, 86e87 V2R-related olfC gene family, 87e88 Terrestrial olfaction, 84e85 See also Amphibian olfaction Tertiary amines, 71 Tetrahymena, 125e126 Tetrapods, 57 TEVC See Two-electrode voltage clamp electrophysiology (TEVC) TGF See Transforming growth factor (TGF) Thermobia domestica (T domestica), 103e104 Thermosensation, 384e385 407 Tip recordings, 250e251 TIRF See Total internal reflection fluorescence (TIRF) Tissue PO2, 323 Titan arum (Amorphophallus titanium), 37f, 39e40 7-TMD See Seven-transmembrane domain (7-TMD) TM domains See Transmembrane domains (TM domains) TMEM67 See Transmembrane protein 67 (TMEM67) Toothed whales, 91 Total internal reflection fluorescence (TIRF), 163 Touhara’s approach, 52 Trace amine-associated receptors (TAARs), 15e16, 68, 84 ecologically salient TAAR responses, 74f expression patterns, 68e70 gene family, 68 ligands and behaviors, 70, 72f biogenic amines, 71 HEK-293 cells, 71 TAAR3, 71e72 TAAR4, 72e73 TAAR5, 73e75 TAAR7s, 75e76 TAAR8c, 76 TAAR9, 76 TAAR13c, 76 tertiary amines, 71 neuron projections to main olfactory bulb in mouse, 77 projections of TAAR-expressing OSNs, 75f TAAR-expressing OSNs, 209 TAAR-expressing sensory neurons in olfactory system, 69f TAAR1, 68 Taar2 coding sequence, 68 TAAR3, 71e72 TAAR4, 72e73 TAAR5, 73e75 Taar6, 70 Taar7a, 68 Taar7b, 68 Taar7c, 68 Taar7d, 68 Taar7e, 68, 76 Taar7f, 68, 76 Taar7s, 70, 75e76 TAAR8c, 76 TAAR9, 76 TAAR13c, 76, 93 Transcriptomics, 103 Transduction machineries, 326b Transduction mechanism, 325 Transforming growth factor (TGF), 344 408 Transgenic expression of centrin2 (CETN2), 161 Transient amino acid receptor (TAAR), 209e210 Transient receptor potential cation channel subfamily M member (TRPM5), 276, 300, 361 Transient receptor potential channel (TRP channel), 197e198, 209, 254b, 259, 378e380 Transient receptor potential channel subfamily A member (TRPA1), 382e383 species-specific variation in, 384f Transient receptor potential channel subfamily V member (TRPV1), 291, 377e378 Transient receptor potential channel subfamily V member (TRPV3), 383e385 Transient receptor potential channel type C2 (Trpc2), 5e6, 91 Transmembrane domains (TM domains), 50e51, 236e237 Transmembrane protein 67 (TMEM67), 164 TRCs See Taste receptor cells (TRCs) Trigeminal nerve, 376 Trimethylamine, 15e16, 73 1,4,5-trisphosphate (IP3), 276 TRP channel See Transient receptor potential channel (TRP channel) TRP channel family M member (TRPM8), 378e380 pharmacology, 381 TRPA1, 382e383 TRPM8-deficient mice, 381 TRPV3, 383e385 TRP-expressing OSNs, 209 TRPA1 See Transient receptor potential channel subfamily A member (TRPA1) Trpc2 See Transient receptor potential channel type C2 (Trpc2) TRPM5 See Transient receptor potential cation channel subfamily M member (TRPM5) TRPM8 See TRP channel family M member (TRPM8) TRPV1 See Transient receptor potential channel subfamily V member (TRPV1) TRPV1t, 291 TRPV3 See Transient receptor potential channel subfamily V member (TRPV3) TWIK-related acid-sensitive K+ (TASK), 327 Two-choice feeding assay, 252e253 Two-electrode voltage clamp electrophysiology (TEVC), 115 Type taste receptors (TAS1Rs), 228, 274e275 Type vomeronasal receptor (V1R), 7, 84, 176e180 functions, 179e180 genes, 177e179 Type taste receptors (TAS2Rs), 233e234, 274e275, 279b INDEX gene repertoires of vertebrates, 233e234 receptive ranges of, 235e236 Type vomeronasal receptor (V2R), 7, 84, 176, 180e182 functions, 181e182 genes, 181 Type vomeronasal receptor (Vmn2R) See Type vomeronasal receptor (V2R) Type IP3 receptor (IP3R3), 276 Type A g-aminobutyric acid receptors (GABAARs), 41b Type I cells, 322, 324, 329e330, 332 Type II cells, 323 Type III adenylyl cyclase (ACIII), 70 U Umami taste, 360e361 receptor(s), 230e231 Urochordates, 57 Utetheisa ornatrix (U ornatrix), 41 V V1R See Type vomeronasal receptor (V1R) V1R-expressing VSNs, 179 V1R-related Ora gene family, 86e87 V2R See Type vomeronasal receptor (V2R) V2R-related olfC gene family, 87e88 V2r2, 193e195 V2Rp5, 10 Vanderbilt University Allosteric Agonist (VUAA1), 106 Vanilloid receptor subtype (VR1), 377 Vanilloid receptor-1 (VR-1) See TRC-specific variant of the transient receptor potential V1 (TRPV1) Vasoactive intestinal peptide (VIP), 300, 306 Ventricle, 339e341 See also CP-CSF system Ventricular system, 339e341 and circulatory pathway of CSF, 340f Venus flytrap domain (VFTD), 228 Vertebrate(s), 326b olfactory system, 82 transduction, 126f ORs bioinformatic analysis, 52e53 genes, 82e84 odor recognition theory, 49e50 putative OR genes, 50e51 VFTD See Venus flytrap domain (VFTD) Vibrational theory, 50 VIP See Vasoactive intestinal peptide (VIP) Vmn1r genes, 90 Vmn1rs, 177e178 INDEX Vmn2r116 (V2rp5), 193e195 Vmn2r26 (V2r1b), 193e195 Vmn2rs, 181 VNO See Vomeronasal organ (VNO) VNO sensory neurons (VSNs), VNO-stimulating ligand families, 10 Volatiles, 31e32 Vomeronasal chemoreceptor function, 193e195 FPR expression, 183 information processing in AOB, 198b Vomeronasal organ (VNO), 4e6, 9, 90, 176, 178, 191 anatomy and cellular composition, 192e193, 192f detecting specialized odors, 14e15 signal transduction mechanisms, 194f vomeronasal chemoreceptor function, 193e195 Vomeronasal receptors (VRs), 7, 176 chemoreceptors, chemical isolation, and speciation, 184b coding lines, 184e185 FPRs functions, 183 genes, 182e183 gene families in mouse, 177f ORs, 183e184 V1Rs, 176e180 functions, 179e180 genes, 177e179 V2Rs, 180e182 functions, 181e182 genes, 181 Vomeronasal receptors type (V1R) See Type vomeronasal receptor (V1R) Vomeronasal receptors type (V2R) See Type vomeronasal receptor (V2R) 409 Vomeronasal sensory neurons (VSNs), 176, 184, 192e193 ion channels mediating secondary signaling events, 196 primary signal transduction pathway(s), 196e199 receptor-dependent transduction pathways, 195e199 secondary signaling processes, 195e199 vomeronasal information processing in AOB, 198b VR1 See Vanilloid receptor subtype (VR1) VRs See Vomeronasal receptors (VRs) VSNs See VNO sensory neurons (VSNs); Vomeronasal sensory neurons (VSNs) VUAA1 See Vanderbilt University Allosteric Agonist (VUAA1) W Water taste, 259 “Whole-sensilla tip recording” method, 250e251 Wild type mice (WT mice), 303, 312b X Xenopus laevis See Clawed frog (Xenopus laevis) Xenopus laevis oocyte expression system, 58 Xenopus tropicalis (X tropicalis), 90 Xt_ora14, 90 Y Yellow fluorescent protein (YFP), 308 Z Z-11e14-acetate, 37e38 Z-5-tetradecen-1-ol (Z5e14:OH), 60 Zhao’s approach, 52 ... detected and converted into a cellular signal is known as chemosensory transduction, and is the subject of this book The study of chemosensory transduction has seen an explosion of knowledge in recent... signs of fear The ability of certain odor blends to act as attractive WHAT IS CHEMOSENSORY TRANSDUCTION? Chemosensory transduction may be defined as the process by which chemical stimulidincluding... subcellular compartments (such as cilia or microvilli) that are optimized for the transduction process In most cases, chemosensory transduction is a multistep mechanism in which biochemical membrane signals