structural and functional organization of the synapse

STRUCTURAL AND FUNCTIONAL ORGANIZATION OF THE SYNAPSE STRUCTURAL AND FUNCTIONAL ORGANIZATION OF THE SYNAPSE Edited by Johannes W Hell University of Iowa Iowa City, IA, USA and Michael D Ehlers Duke University Medical Center Durham, NC, USA 13 Editors Johannes W Hell Department of Pharmacology 2-512 BSB University of Iowa Iowa City, IA 52242 Michael D Ehlers Department of Neurobiology Duke University Medical Center Box 3209 Durham, NC 27710 ISBN: 978-0-387-77231-8 e-ISBN: 978-0-387-77232-5 DOI: 10.1007/978-0-387-77232-5 Library of Congress Control Number: 2007941249 © 2008 Springer Science+Business Media, LLC All rights reserved This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied, with respect to the material contained herein Cover illustration: The cover illustration shows an immunofluorsecence micrograph of a hippocampal pyramidal neuron at two weeks in culture The neuron was stained for the abundant calcium and calmodulin-dependent protein kinase CaMKII (green) and the presynaptic protein synapsin (red) The pictures was provided by Y Chen and J W Hell, University of Iowa Printed on acid-free paper springer.com With special dedication to our late friend and colleague Alaa El-Husseini Preface The synapse is a fascinating structure for many reasons Biologically, it is an exquisitely organized subcellular compartment that has a remarkable capacity for fidelity and endurance Computationally, synapses play a central role in signal transmission and processing that represent evolution’s solution to learning and memory Nervous systems, including our own brains, possess an extraordinary capacity for adaptation and memory because the synapse, not the neuron, constitutes the basic unit for information storage Because the molecular complexities underlying signal processing and information storage must occur within the tiny space of the synapse, the precise molecular organization of proteins, lipids, and membranes at the synapse is paramount Given the central role of the synapse in neuronal communication, it comes as no surprise that dysregulation of the synapse accounts for many, if not most, neurological and psychiatric disorders Clinically, the synapse thus constitutes a prime target for treatments of these diseases It is for these reasons that we have chosen to focus our work on deciphering the structural and functional organization of the synapse We have assembled leaders in the field of synapse biology to describe and distill the wonders and mysteries of the synapse This book provides a fundamental description of the synapse developed over many decades by numerous investigators, paired with recent insight into new aspects of synapse structure and function that is still in flux and at the cutting edge of research This book grew out of a symposium and a research seminar at the University of Iowa that were sponsored, in large part, by the generous support of the Obermann Center for Advanced Studies Obermann Seminars are specifically designed to gather international scholars and produce interdisciplinary research publications We are grateful for the exceptional efforts of our contributing authors, without whom this book would not have been possible Their willingness to take time from their busy research schedules to share their insight and ideas with the breadth and depth that allow us to compile a collective work that is illuminating and useful, for both the general biologist and specialized neuroscientist, is very much appreciated We express our gratitude to our assistants Ms Susan Harward and Ms Sue Birely for their professionalism and help with the book layout and proof reading Lastly, we would like to thank our families (Laura and Henrik, Mary, Solon, Anselm, and Hans), who provided the support, encouragement, inspiration and comic relief, that in many ways helped to make this book possible Michael D Ehlers and Johannes W Hell Editors Contents List of Contributors xiii Diversity in Synapse Structure and Composition Kristen M Harris The Role of Glutamate Transporters in Synaptic Transmission 23 Dwight E Bergles and Robert H Edwards Structure and Function of Vertebrate and Invertebrate Active Zones .63 Craig C Garner and Kang Shen Neurotransmitter Release Machinery: Components of the Neuronal SNARE Complex and Their Function 91 Deniz Atasoy and Ege T Kavalali The Molecular Machinery for Synaptic Vesicle Endocytosis 111 Peter S McPherson, Brigitte Ritter, and George J Augustine Initiation and Regulation of Synaptic Transmission by Presynaptic Calcium Channel Signaling Complexes 147 Zu-Hang Sheng, Amy Lee, and William A Catterall Adhesion Molecules at the Synapse 173 Alaa El-Husseini Dendritic Organelles for Postsynaptic Trafficking .205 Cyril Hanus and Michael D Ehlers Structure and Mechanism of Action of AMPA and Kainate Receptors 251 Mark L Mayer Cellular Biology of AMPA Receptor Trafficking and Synaptic Plasticity 271 Jose A Esteban x Contents Structure and Function of the NMDA Receptor 289 Hongjie Yuan, Matthew T Geballe, Kasper B Hansen, and Stephen F Traynelis Molecular Properties and Cell Biology of the NMDA Receptor 317 Robert J Wenthold, Rana A Al-Hallaq, Catherine Croft Swanwick, and Ronald S Petralia Surface Trafficking of Membrane Proteins at Excitatory and Inhibitory Synapses 369 Daniel Choquet and Antoine Triller Scaffold Proteins in the Postsynaptic Density 407 Mary B Kennedy, Edoardo Marcora, and Holly J Carlisle Ca2+ Signaling in Dendritic Spines .441 Bernardo L Sabatini and Karel Svoboda Postsynaptic Targeting of Protein Kinases and Phosphatases 459 Stefan Strack and Johannes W Hell Long-Term Potentiation 501 John E Lisman and Johannes W Hell Homeostatic Synaptic Plasticity 535 Gina G Turrigiano Ubiquitin and Protein Degradation in Synapse Function 553 Thomas D Helton and Michael D Ehlers Signaling from Synapse to Nucleus 601 Carrie L Heusner and Kelsey C Martin Molecular Organization of the Postsynaptic Membrane at Inhibitory Synapses 621 I Lorena Arancibia-Carcamo, Antoine Triller, and Josef T Kittler Acid-Sensing Ion Channels (ASICs) and pH in Synapse Physiology 661 John A Wemmie, Xiang-ming Zha, and Michael J Welsh Glia as Active Participants in the Development and Function of Synapses 683 Cagla Eroglu, Ben A Barres and Beth Stevens Plasticity of Dentate Granule Cell Mossy Fiber Synapses: A Putative Mechanism of Limbic Epileptogenesis 715 James O McNamara, Yang Z Huang, and Enhui Pan Contents xi Stroke – A Synaptic Perspective 731 Robert Meller and Roger P Simon Neuroplasticity and Pathological Pain 759 Michael W Salter Index .781 List of Contributors Rana A Al-Hallaq Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD, USA, e-mail: wenthold@nidcd.nih.gov I Lorena Arancibia-Carcamo Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK, e-mail: l.carcamo@ucl.ac.uk Deniz Atasoy Department of Neuroscience, U.T Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9111, USA, e-mail: ege.kavalali@utsouthwestern.edu George J Augustine Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, NC 27710, USA, e-mail: georgea@neuro.duke.edu Ben A Barres Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA, e-mail: barres@stanford.edu Dwight E Bergles The Solomon H Snyder Department of Neuroscience, Johns Hopkins School of Medicine, 725 N Wolfe St., WBSB 1003, Baltimore, MD 21205, USA, e-mail: dbergles@jhmi.edu Holly J Carlisle Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA, e-mail: carlisle@caltech.edu William A Catterall Department of Pharmacology, University of Washington, Seattle, WA 98195-7280, USA, e-mail: wcatt@u.washington.edu Daniel Choquet UMR 5091 CNRS, Université de Bordeaux 2, Physiologie Cellulaire de la Synapse, Institut Franỗois Magendie rue Camille Saint Saởns 33077 Bordeaux Cedex, France, e-mail: dchoquet@u-bordeaux2.fr Index Excitatory postsynaptic current (EPSC), 289 Excitatory post-synaptic potential (EPSP), 165, 501 in dorsal horn neurons, 760 potentiation, 672 Excitatory presynaptic boutons, Excitatory synapses function on principal neurons, 717 scaling of, 540–541 transmission in mammalian brain, 175 Exo70 mutant overexpression, 225 Exocyst complex expression in mammalian nervous system, 225 Extracellular Mg2+voltage-dependent channel block, 301 Extracellular pH at synapse alkalosis and neurotransmission, 662–663 neural activity and acidosis, 663–664 neurological disease and, 664 proton release and, 661–662 Extracellular Zn2+and neuronal NMDA receptors, 303 Extrasynaptic NMDARs, distribution and function, 332–333 Eyman, M., F0/F1-ATPase, 27–28 F-actin network of cell cortex, 224 Fairman, W.A., 43–44 Fascicilin II invertebrate molecules, 186 Fast-spiking (FS) basket cells, 546 F-box protein (Fbx2), 329 F-box protein FSN–1, 81, 569 Ferrara, E., Fes/CIP4 homology (FCH), 128 Fiala, J.C., 8, 13, 175 Fibroblast growth factor receptor (FGFR)-mediated signaling, 190 Fibronectin type III repeats, 190 Fischbach, G.D., 41 Fischer, F., 29 Focal stroke syndrome, 732 Foot-in-the-door blockers, 302 FRAP approach and synaptic molecules dynamics, 379, 383 Fremeau, R.T., 31 Frequency-dependent neuron-glia signaling, 700 Frog neuromuscular junction (NMJ), AZs studies of, 70–71 787 Full-length Usp14 transgene expression in brain, 572 Function-blocking TrkB antibody and TrkB-Fc, 772 Furness, D.N., 37, 45 FXDXF protein binding, 125 Fyn kinase, 328 GABA-and glycinergic inhibition in dorsal horn, 772–773 GABA and NMDA receptors, 338 GABAA receptor associated protein (GABARAP), 643 GABAA receptors cell surface, diffusional properties of, 645–646 membrane trafficking and dynamics of, 641–644 mobility dynamics, 387 molecular heterogeneity of, 625–627 molecular identification of, 624 pharmacology of, 623–624 structure of, 627–628 trafficking of, 579, 642 GABAB-receptor-mediated elevation of calcium in astrocytes, 704 GABAergic miniature inhibitory postsynaptic currents (mIPSCs), 635 GABAergic projection medium-sized spiny neurons (MSNs), 340 GABAergic synapses overexpression in hippocampal neurons, 179–180 GABA release and glutamate transporters, 46 Gahwiler, B.H., 39 Ganel, R., 46 Gap junction hemichannels in astrocytes, 704 Garner, C.C., Genetically encoded Ca2+ indicators (GECIs), 450–451 Genoud, C., 6, 45 Gephyrin, scaffolding protein, 180 molecular organization of inhibitory synaptic domains role in and proteins, 634–635 structure and lattice formation, 632–634 Gerber, U., 39 Gershon, M.D., 29, 38 GFP-tagged receptors, time-lapse imaging and photobleaching of, 218–220 788 Index Ginsberg, S.D., 45 GKAP/SAPAP family, see Guanylate kinase-associated proteins GKAP, see Guanylate kinase-associated protein GK-associated proteins (GKAPs), 414 linking shank with PSD–95, 411 and postsynaptic scaffolding proteins, 178 and SAPAP scaffold proteins, 408 Shank-cortactin-actin, 330 GLAST (EAAT1) and synapses uptake, 44 Glia in synapses development and function of, 683–684 maintenance and structural plasticity, 694–697 and mature CNS, 698–699 neural circuits, elimination and refinement of, 693–694 types of cells, 685–686 Glial fibrillary acidic protein (GFAP), 685 Glia-neuronal signaling at synapse, 703–705 Glia role in synaptic plasticity, 705–707 Glia to glia signaling, 701–703 Gliotransmitters activity-dependent release and synaptic activity in neurons, 698 Global brain ischemia, 732 Glowatzki, E., 45 GLT-1 transporter currents in outside-out patches, 41 GLUE, see GRAM-like ubiquitin-binding in EAP45 GluR1-binding protein SAP97 (SynapseAssociated Protein 97), 274 GluR1-GluR2 hetero-oligomers, 272 GluR1 phosphorylation by PKA and CaMKII activation, 275 GluR2 apo structure, 257 GluR2-GRIP interaction and AMPA receptors at synapse, 181 GluR2-lacking AMPA receptors, 509 GluR4-containing AMPARs, 272 GluR6, SUMOylation of, 579 MGluRs activation at recurrent synapses onto CA1 interneurons, 44 Glutamate evoked transporter currents, 42 excitotoxicty and ischemia, 734–735 exocytotic release from preformed synaptic vesicles, 23–25 gated chloride channel, 47–48 neurotransmitter, 257 receptor internalization, 373 receptor regulation in C elegans, 577 synaptically released and excitotoxicity after ischemia, 736 uptake at cell surface, 38–39 astroglial transport and, 44–46 EAAT3 role for, 46–47 glutamate-gated chloride channel, 47–48 glutamate transporters localization of, 43–44 synapses from, 39–42 transients at cerebellar synapses, 47 Glutamate/aspartate transporter (GLAST), 698 Glutamate receptor interacting protein (GRIP1), 218, 636–637 Glutamate receptor ion channels (iGluRs) agonist binding site, 257–259 desensitization mechanism, 255–257 domain organization and activation mechanism for gating, 252 extracellular ions, modulation by, 263–266 ligand binding domains of, 253–255 ligand binding and subtype pharmacology, 259–261 partial agonist activity, mechanism of, 261–263 structure of, 251 Glutamate transporter (GLT1), 698 Glutamic acid decarboxylase (GAD), 175 Glutamine binding protein (QBP), 292 Glutamine glutamate cycle, 26 Glycine receptors assembly and composition of plasma membrane receptors of, 628–629 cell surface, diffusional properties of, 645–646 membrane trafficking and dynamics of, 641–644 molecular identification of, 624 pharmacology of, 623–624 structure of, 627–628 subcellular localization and, 629–630 and subunit isoforms, 624–625 Glycosylation and neuroligin/neurexin interaction and function, 183–184 O-Glycosylation cassette and neuroligins, 178–179 Glycosylphosphatidylinositol (GPI) anchor, 190, 215 Index GlyR-gephyrin interaction, 395 Golgi apparatus and membrane trafficking, 220 Golgi markers galactosyltransferase, 211 trans-Golgi-network, 206 trans-Golgi network, 321 TGN-derived vesicles at neuron, 211 Golgi/TGN and clathrin-coated vesicles, 323 GPCR signaling cascade upstream of SFK-mediated NMDAR upregulation, 766 G-Protein coupled receptor mGluR1, 292 G-protein coupled receptors (GPCRs), 226 G-protein coupled signaling cascades in Schwann cells, 703 Gq-coupled receptor in astrocytes, 704 Gq-type G-proteins and phospholipase C (PLC), 443 GRAM-like ubiquitin-binding in EAP45, 562 GRASP65 overexpression, 217 Gray, E.G., 69 Green fluorescent protein (GFP) variants, 372 Grewer, C., 38 GRIP1-AMPAR complex, 273 GRIP1/KIF5 interaction in dendrite development, 218 GRIP/ABP/GluR2 complex, 419 GRIP/ABP and GRIP-like family, 408 GRIP/ABP-PICK1 interactions, 280 GRIP proteins, scaffolding molecules, 181 Groves, P.M., GTPase activating proteins (GAPs), 223 Guanine nucleotide exchange factor (GEF), 129 collybistin, 634 Guanylate kinase-associated protein, 330, 408 Gundersen, V., 34 Gyo, K., 45 H+ electrochemical gradient for cytosolic transmitter, 26 chloride flux, 28–29 regulation of, 29 vacuolar H+ pump, 27–28 Hakuba, N., 45 Hall, A.K., Harris, K.M., 8, 12, 14, 15, 175 Hart, S.A., Hartveit, E., 47 Hasegawa, J., 73 789 Hashimoto, K., 174 Hausser, M., 39, 42 Haydon, P.G., Hediger, M.A., 46 Hepatocyte-growth-factor-regulated tyrosine-kinase substrate (Hrs), 562 Hermaphrodite-specific motor neuron (HSNL), 571 Hestrin, S., 44 Heuser, J.E., He, Y., 43 Hiel, H., 45 High-affinity NMDA receptors, 24 Hippocampal CA1 synapse, ultrastructural features of presynaptic active zone from, 70 Hirling, H., 45 Histocompatibility complex (MHC) class I and II, 769 HLFY motif function, 320 Holmseth, S., 44 Holtje, M., 35 Homeostatic synaptic plasticity mechanisms, 536 cell-autonomous forms of, 537 at neuromuscular junction (NMJ), 537–538 Homer-mGluR5, scaffolding protein Homer, 391 Homologous to E6-AP carboxyl terminus (HECT), 554 Hori, S., 26, 44 Hrs-ubiquitin-interacting motifs (UIM), 561 Hsc70 in CCV uncoating, 133–134 Huang, Y.H., 43, 44, 47 Hull, C., 47 Huntingtin associated protein (HAP1), 644 Huntingtin-interacting proteins (HIPs), 129–130 Huntington’s disease and dendritic membrane trafficking, 233 and NMDA channel blockers, 302 NMDAR trafficking, 340–341 Hurlburt, J.L., 16, 229 6-Hydroxydopamine (6-OHDA), 342–343 Ichihara, N., 26, 44 Iino, M., 47 Importin-mediated transport functions, 609 Influenza HA protein (apical/axonal), 215 Inhibitor of apoptosis protein (IAPs), 736 790 Index Inhibitory ligand gated channels structure, 622 Inhibitory post-synaptic potentials (IPSPs) mediated by GABAA and glycine receptors, 761 Inhibitory presynaptic boutons, Inhibitory synapses cell adhesion molecules neurexins and neuroligins, 637–639 components of, 630–631 molecular organization, 621 transmission in dorsal horn, 761 Inositol triphosphate receptors (IP3R) activation, 210 Inoue Y., 34 Intersectin-l, 130 Intracranial aneurysm, 732 Invertebrate synapses, 69–72 Ion permeation, structural determinants of, 298–300 Irwin, N., 43 Isaacson, J.S., 39 Ischemia and excitotoxicity, 734–735 Iwama, H., 26, 44 Jabaudon, D., 39 Jahn, R., 4, 35, 36 Jahr, C.E., 38, 40, 42, 44, 46–47 Janssen, W.G., 43 Janzen, J., 46 Jin, L., 43–44, 46 Jin, L.A., 46 K+ channels with tetraethylammonium (TEA), 467 Kainate receptors anion binding site, 265 Kainate-type glutamate receptors (KRs), 443 Kakegawa, W., 47 Kalirin7, guanine nucleotide exchange factor (GEF), 413 Kalloniatis, M., 40 Kanai, Y., 46, 73, 218 Kano, M., 45 Kaplan, B.B., KA subtype kainate receptors, 257 Katagiri, H., 44 Kavanaugh, M.P., 34, 43, 47 Kawashima, N., 26, 44 KcsA channel, 410 KcsA and MthK channels structures, 301 Kennedy, M.B., 12 Ketamine, trapping blockers, 302 KIF17 complexes, 323 KIF1a kinesin motor, SV precursors trafficking, 76 KIF1/UNC-104 family of motors and SVs trafficking, 73 Kikuchi, T., 26, 44 Kim, Y.S., 43 Kinesin family and axonal transport, 218 Kirov, S.A., 8, 9, 175 Kish, P.E., 29 Kitai, S.T., Klingauf, J., 44 Knott, G.W., 6, 32 Koga, K., 45 Komine, O., 47 Kuhar, M.J., 38 Kuncl, R.W., 46 L650T mutant complex with kainate, 262 LAR receptor protein tyrosine phosphatases (LAR-RPTPs), 570 Latency-associated protein (LAP), 692 Lateral superior olive (LSO) switch from GABA to glycine, 32 Latrunculin treatment of hippocampal cells, 741 L-DOPA-induced dyskinesia, 343 Lehre, K.P., 43, 44, 45 Levey, A.I., 46 LINGO, leucine-rich repeats (LRRs), 187 Lipid phosphatase synaptojanin, 37 Liprin/SYD-2 structure, 75–76 Lisman, J., 12 Liu, W.L., 40 Local protein synthesis in dendrites and spines, 13 Long-range targeting and synapses microtubule transport, 217–218 polarized trafficking and, 214 asymmetric dendrite outgrowth, 216–217 asymmetric protein, 215–216 Long term depression (LTD), 279 and postsynaptic glutamate uptake, 47 Long-term potentiation (LTP), 190, 501–502 CaMKII role in maintenance of, 516–517 evoked by Schaffer collateral fiber stimulation, 672 expression of molecular mechanisms of postsynaptic, 509–513 Index presynaptic and postsynaptic, 507–508 induction of Ca2+ entry and NMDA receptor, 504–506 Ca2+ sensors for, 506–507 in Hebbian plasticity, 504 NMDA receptors and, 503 integrated model of pre-and postsynaptic, 513–515 late phase of, 518–520 modulatory effects on, 520–521 PKMζ role in maintenance of, 517–518 postsynaptic and trans-synaptic growth process, 513–515 properties of Hebbian synaptic modification, 503 synapse specificity and associativity, 501–502 Low-affinity AMPA receptors, 24 LTP-expression at Schaffer collateral/CA1 synapses in hippocampal slices, 230 L-type Ca2+ currents, synaptic transmission at ribbon synapses, 148 Lysine/arginine/ornithnine-binding protein (LAOBP), 292 Madin-Darby canine kidney (MDCK) cell-line, 215 Maeno, H., 47 Magistretti, P.J., Mahadomrongkul, V., 43 Malherbe, P., 41 Manabe, T., 44, 507 MAP kinase pathway, 330 MAP kinases Erk and activation, 417 Marcaggi, P., 45 Marc, R.E., 40 Martin, L., 46 Martin, L.J., 45 Martin, R., Mathews, G.C., 46 Mature hippocampus, inhibitory symmetric synapses in, Medial nucleus of trapezoid body (MNTB), 32 Melone, M., 46 Membrane-anchored receptors, 378 Membrane-associated guanylate kinase-like proteins (MAGUK family), 323–324, 408 791 and postsynaptic scaffolding proteins, 178 scaffolding proteins of, 279 Membrane protein internalization mechanism, 225 Membrane proteins surface trafficking of excitatory and inhibitory synapses, 369 diffusion rates of, 383–385 receptor endocytosis and, 373–374 exocytosis and, 371–373 receptor mobility tracking and compartments transition and dwell time within, 380–382 fluorescence recovery after photobleaching, 375 labelling of, 379 label size, effect of, 378 ligands, 377–378 live imaging of, 383 pointing accuracy of, 379–380 single particle tracking, 375–377 trajectory reconstruction and analysis, 380 and subunit specific properties, 385–386 glutamate receptors, 387 glycine and GABA, 387–388 Membrane trafficking pathways in eukaryotic cells, 207 Metabotropic-glutamate receptors (mGluRs), 408, 443 Metaplasticity, see Long-term potentiation (LTP) N-Methyl-D-aspartate (NMDA) amplitude receptor mediated responses in CA1 pyramidal neurons, 44 channel activity by phosphotyrosine phosphatase (STEP), 766 glutamate-receptor channels, 175 potentiation, 544 receptors, 271 molecular architecture of, 292–293 subunit diversity of, 289–291 reduced excitotoxicity in rapid ischemic tolerance, 750 addition and removal, 325–328 and adhesion molecules, 330–331 modification of, 328–329 PDZ proteins interactions with, 329–330 trafficking and disease Alzheimer’s disease, 341–342 792 Index excitotoxic cell death and, 339–340 Huntington’s disease, 340–341 Parkinson’s disease, 342–343 Schizophrenia and mood disorders, 344–345 trafficking at synapse in mature forebrain, 326 Microglia-neuron signaling and transmission after peripheral nerve injury, 769–770 BDNF role of, 771–772 disinhibition and NMDAR synaptic transmission, 772–773 Microtubule associated protein GABARAP, 636 Microtubule associated proteins, 741 Microtubule organizing center (MTOC), 217 Minelli, A., 46 Mint-1 and neurexins, 183 Mint, active zone scaffolding proteins, 157 Mint protein, 67 Mishra, A., Mitochondria, dendritic, 214 Mitogen-activated protein kinase (MAPK) pathway, 767–768 Miyazaki, T., 34 MK-801, trapping blockers, 302 Modified C–terminal in-between (IBR) RING, 580–581 Monod Wyman Changeux models of allostery, 261 Morkve, S.H., 47 Morrison, J.H., 43 Mossy fiber-CA3 pyramid synapse, 725 Mossy fiber synapses plasticity in animal models of epileptogenesis, 724–725 projection to CA3, anatomical and physiological studies, 722–724 TrkB and, 725 mPins expression, 324 MPTP primate model of PD, 343 Müller cells and tetrodotoxin (TTX), 700 Multisynaptic dendritic spines, Multivesicular endosome/multivesicular body (MVE/MVB) for degradation, 563 Multivesicular endosomes (MVE)/ multivesicular bodies (MVB), 562 Munc–13 AZ proteins, 68 vesicle priming protein, 573 Murdoch, G.H., 44 Muscle-specific receptor tyrosine kinase (MuSK), 570 mediated nicotinic acetylcholine receptor, 571 Mushroom spines with spine apparatus, 15 Myelin associated glycoprotein (MAG), 697 Myosin motors, 223–224 Myosin VI, actin regulatory proteins, 227 Myotubular myopathy related (MTMR), 134 Nash, N., 46 nCaBP and Cav2, channels, 163 NECAP, 1, 2, see Adaptin ear binding coat associated protein Neep21 function in activity-dependent recycling of AMPA receptor, 229–230 Nerve growth factor (NGF)-deprived sympathetic neurons, 568 Netrin G ligands (NGLs), 187–188 Neural cell adhesion molecule (NCAM), 190 Neuregulin activity and NMDAR activation, 344 Neurexins, brain-specific proteins, 177 trans-synaptic signaling at glutamatergic synapses, 178 Neuroligins, synaptic cell adhesion molecules, 177 differential mobility at synaptic sites, 182 inhibitory synapses maturation of, 179 in neurons overexpression of, 180 trans-synaptic signaling at glutamatergic synapses, 178 Neuronal migration and neurite outgrowth, 337–339 Neuronal potassium channels, polarized trafficking, 216 Neuronal secretory pathway, 208 Neuron-enriched endosomal protein of 21 kDa (Neep21), 229–230 Neuron-glia, activity-dependent communication at synapse, 698–699 Neuron and glia communication, 699–700 Neurons, cell biological mechanisms for transmitting signals in axons, 603 Neuron-specific actin-binding protein profilin-IIa, 413 Neuroplasticity and pathological pain, 759 Neurotransmitter from synaptic vesicle, 24 Index NG2-positive oligodendrocyte progenitor cells (NG2 cells) and neurons, communication between, 701 NGL, leucine-rich repeats (LRRs), 187–188 Nico, B., 12 Nicoll, R.A., 34, 36 Nicotinamide mononucleotide adenylyltransferase (Nmnat), 568 Nicotinic acetylcholine receptors trafficking, 579 Nimchinsky, E.A., 42 Nishikawa, T., 26, 44 NLRR, leucine-rich repeats (LRRs), 187 NMDAR endocytosis and dileucine motif (LL), 327 Nogo-66 receptor, leucine-rich repeats (LRRs), 187 Nogo-66 receptor (NgR), 697 Nogo, melin proteins, 697 Non-docked vesicle, Non-synaptic boutons, NR1–3 splice variant, C1 and C2’ cassettes, 320 NR1/NR2A/NR2B receptors in hippocampal neuron synapses, 318 NR1/NR2B receptors, 299 NR1/NR2B recombinant receptors, 305 NR1/NR2D receptors, 290–291 NR2A-binding protein α 1-chimerin and GTPase-activating (GAP) domain, 337 NR2A-containing recombinant NMDA receptors, 303 NR2A-and NR2B-containing NMDARs, 332, 340 and CaMKII, 337 NR2B co-expression with mutant htt in HEK293 cells, 340–341 NR2B-containing NMDA receptors, 325, 330 in piriform cortex, 326 and synapses, 218 NR2B subunit tyrosine-based YXXΦ consensus motif, 327 NR3A-containing NMDARs endocytosis, 333 NSF-mediated dissociation of GluR2-PICK1 complex, 280 N-type Ca2+ channels, G-protein inhibition, 159 N-type calcium channels and NMDARs, 338 Nunez, E.A., 29 793 Obara, T., 48 Oertner, T.G., 42 Ogawa, S., 45 Okuyama, S., 44–45 Oliet, S.H., 46 Oligodendrocyte-myelin glycoprotein (OMgp), 697 Oligodendrocyte precursor cells (OPCs) role at synapse, 685 Oligomerization and neuroligin/neurexin interaction and function, 183–184 Open conformation syntaxin-1 SNARE motif, 94 Orth, C.B., 14 Oshima, T., 42 Ostroff, L., 12, 175 Ostroff, L.E., 13 Otis, T.S., 39, 42, 47 Otmakhov, N., 12 Ottersen, O.P., 25, 35 Ozawa, S., 45 P2X7 ATP receptor in astrocytes, 704 P2X family of ligand-gated ion channels activated by ATP, 770 PACSIN1/syndapin1adaptor and C–terminal of NR3A, 333 PACSIN-1/syndapin-1, endocytic adaptor, 227 Pahner, I., 35 Palay, S.L., 12 Pam/highwire/RPM-1 (PHR) family of ubiquitin ligases, 569 Parallel fiber axons synapse with dendritic spines of Purkinje cell spiny branchlets, Pardo, C.A., 46 Parkin, RING class of E3 ligases, 580 Parkinson’s disease and NMDA channel blockers, 302 NMDAR trafficking and, 342–343 Park, M., 17, 175 PD 6-OHDA lesion model, 343 PDZ-binding motif, PSD-95 and SAP102 interaction, 225 PDZ domain-containing protein glutamate receptor interacting protein (GRIP1), 273 PDZ domain containing RING finger (PDZRN3), 570 794 Index PDZ domain protein and PICK1 (Protein Interacting with C-Kinase 1), 272 PDZ-domains containing scaffold protein MUPP–1, 416 PSD-95 family and, 411–412 scaffold protein PSD–95, 391 PDZ interaction of NR2B and mLin–7, 323 Peghini, P., 46 Peripheral nerve injury and pain hypersensitivity, 769–770 pain hypersensitivity model for, 773 Perisynaptic astroglial processes, 18–19 Perisynaptic Schwann cells (PSCs), 685 role in synapse formation in PNS, 691–693 Peters, A., 12 Petrak, L.J., Petrini, E.M., 24 Phencyclidine (PCP), trapping blockers, 302 Phenylalkylamines channel antagonists, 147 Phenylethanolamine ifenprodil, subunitselective antagonist, 306–307 Phosphatases targeting to postsynaptic sites, 474–475 protein phosphatase PP1, 475–476 Phosphatidylinositol-3-phosphate (PtdIns3P), 562 Piccolo protein, 7, 67 Pickel, V.M., 31 Piet, R., 46 PKC-dependent endocytosis assays, 573 PKC/MAP kinase pathways, 512 PKC, Pyk2, Src to PSD-95 and ND2 binding, 474 Pleckstrin homology (PH), 119 Pleiomorphic vesicles, P38 MAP kinase pathway, 81 Pohorille, A., 12 Point spread function of optical pathway (PSF), 379 Polarized post-Golgi trafficking, 217 Polo-like kinase (Plk2), 571 Polyribosomes, 13 Porter, C.W., 42 Post-endocytic recycling in synaptic remodeling, 229 Post-ER membrane trafficking, 211 Post golgi sorting and dendritic trafficking organelles packaging, 321–322 Postsynaptic accumulation and CaMKII autophosphorylation, 468–469 endogenous CaMKIIα and β, 467 Postsynaptic cargo, local trafficking role in, 229 Postsynaptic components, local trafficking of dendritic exocytosis exocyst, 224–225 myosin motors and micron-range trafficking of spine cargo, 223–224 and post-endocytic sorting, 225–232 Rab proteins and, 223 regulated exocytosis, postsynaptic membrane, 221–223 Postsynaptic dendritic spine structure diversity in, 10 Post-Synaptic density proteins 95 and 93 (PSD95 and PSD93), 276, 571 Postsynaptic density (PSD), 12, 175, 333 Post-synaptic glutamate receptor activation, 745 Postsynaptic kinase targeting CaMKII and, 460–465 Postsynaptic PDZ domain-containing scaffold proteins, 413 Postsynaptic protein levels, 576 Postsynaptic scaffold proteins with AMPA-type glutamate receptors GRIP/ABP, PICK1, and NSF, 418–419 SAP97 and SAP102, 419–420 Stargazin and PSD, 95, 420 classification of, 408–409 NMDA receptor and, 409–410 PSD-95 family, 411 Postsynaptic scaffold proteins with NMDA receptor PSD-95 family AMPA receptors, 413 Ca2+-regulated enzymes, 412 complexes of, 412 guanylate kinase-like (GK) domain and linkage, 414 with PSD, 414 small GTPase proteins, 412–413 signaling proteins with tails of subunits Ca2+/calmodulin-dependent protein kinase II, 415–417 RasGRF1, 417–418 Post-TGN transport of secretory cargo to plasma membrane, 223–224 Poulain, D.A., 46 Pow, D.V., 43 Index PP1 synaptic targeting by spinophilin and neurabin, 476–478 PP2A and localization in neurons, 479–483 P/Q-type Ca2+ currents in synapses, 150–151 Presynaptic active zones molecular components of, 68 ultrastructural organization of, 69–72 Presynaptic assembly regulation by ubiquitin mediated pathways Rpm-1/highwire and, 80–81 SCF complex, 81 Presynaptic axons axonal bouton, structures and composition, active zone and vesicles, inhibitory synapses, and shapes of postsynaptic dendritic spines, diversity in trajectory of, small dense core vesicles as active zone transporters, Presynaptic AZ proteins, 79–80 Presynaptic boutons, 64 Presynaptic calcium channels and SNARE proteins spatial co-localization and synaptic vesicle release machinery, 151–152 Presynaptic CaV2 channels regulation by calmodulin-like Ca2+-binding proteins Cav1 channels regulation by CaBP, 164–165 Cav2, channels regulation by CaBP, 163–164 and synaptic vesicle fusion machinery, physical and functional coupling of, 152 Presynaptic ephrin-B, 331 Presynaptic exocytosis function, 75 Presynaptic GABA-B autoreceptors on interneurons, 521 Presynaptic NMDARs effect on synaptic transmission, 331 Presynaptic regulation of quantal size activity and, 37–38 neurotransmitter and synaptic vesicle cycles, relationship between, 36 set point, 35–36 thermodynamic equilibrium, 33 transporter expression and leak, 33–35 vesicle volume, changes in, 36–37 795 Presynaptic structure, cellular and molecular assembly of, 73 Presynaptic subcompartments, 65–66 Presynaptic superior cervical ganglion neurons, 155 Presynaptic voltage-gated Ca2+ (Cav) channels, 147 Price, D.L., 45 Pro-cell death protein Bax activation, 735–736 Protein complexes, association with glutamate receptor by scaffold protein homer, 420–421 IP3R and Shank/proSAP linkage, 421 G-Protein coupled receptors (GPCRs), 443 Protein kinase scaffold AKAP-79/150, 414 Proteins interaction sites of CaV2, channels, 153–154 machinery in postsynaptic density, 410 trafficking and neuropathology of AD, 342 Protein tyrosine phosphate binding (PTB), 119 Protocadherins and synapse maturation, 188–189 PSD-93/Chapsyn-110 scaffold proteins, 408 PSD-95 family proteins citron, 330 overexpression of, 411 recruitment of endogenous neuroligin–1, 183 scaffold protein, 407 synaptic scaffolding proteins, 225 PSD-95-SPAR-actin, 330 PSD area, spine volume, and t number of presynaptic vesicles, correlation between, 12 PSD remodeling, UPS-dependent, 575 PSD scaffold proteins domain structures, 409 PTEN ( PtdIns(3)-phosphatase), 133 Purkinje neurons in cerebellum, EAAT4 expression, 43 spines of, 210 Q-SNAREs glutamines, 94 Quairiaux, C., 6, 45 Quantal transporter-mediated anion currents, 47 Qureshi, T., 34 796 Index Rab11a mutants overexpression, 230 rab-3 gene mutations, 74 Rab-dependent exocytic trafficking, 279 Rab family GTPases, membrane trafficking and vesicular fusion, 223 Rab-Interacting Molecule (RIM) and synaptic plasticity, 159 Rabphilin and AZ protein RIM, 74 Rab-specific guanine nucleotide exchange factors (GEFs), 223 Rachakonda, S., 35 Rafiki, A., 34 Rafiq, A., 46 Raiguel, S.F., 40 Rapid ischemic tolerance, 748 Rapid synapse-nucleus signaling action potentials and, 604–605 distal compartments between, 610–611 injury and regeneration, 614–615 retrograde signaling by signaling endosomes, 607–608 synapse development during, 610–612 synaptic plasticity during, 612–614 via endoplasmic reticulum, 605–606 rasGRF1, see ras-specific GDP/GTP exchange factor (GEF) Ras-specific GDP/GTP exchange factor (GEF), 417 Rat cerebellar cortex, reconstructed axons from, Rauen, T., 43 Real, E., Really interesting new gene (RING) domains, 554 Receptor-linker-probe complex, 377 Receptors activity-dependent tuning of recycling kinetics, 229 exocytosis and endocytosis, 370–374 exocytosis, real-time measurements of, 372 mobility of, 374–375 scaffold interactions and cytoskeleton, surface trafficking, 388–392 surface trafficking and synaptic plasticity, 393–394 tracking by labeling methods, 376 trafficking from synthesis and insertion in synapse, 371 Receptor tyrosine kinases (RTKs), 562 Recombinant GluR1-homomeric AMPA receptors, 507 Reese, T.S., Regan, M.R., 43, 581 Regehr, W.G., 18, 39 Regular-spiking non-pyramidal (RSNP) neurons, 546 Reimer, R.J., 31 Retinal-tectal system and N-cadherin function, 188 Retina neurons, EAAT5 expression, 43 Rho effector ROCK-II, 413 Ribatti, D., 12 Ribbon synapses, 78–79 Richerson, G.B., 24 Riedel, D., 41 RIMs protein, 67, 68 RING finger protein highwire, fat facets overexpression, 80 Rizzoli, S.O., Rme1/EHD1 mutants overexpression, 230 RNAi knockdown of CPG2 (candidate plasticity gene 2), 333 RNA interference (RNAi) and GRIP1 expression in dendrites, 218 Rosenberg, P.A., 43 Rossi, D.J., 42 Rostaing, P., Roth, A., 42 Rothstein, J.D., 43, 45, 46 Roundabout (Robo) and DCC/Frazzled (Fra) receptors, 564 R-SNARE arginine, 94 Rusakov, D.A., 45 RXR, ER retention motif, 320 Sabatini, B.L., 42 Sad-1 loss-of-function mutants, 77 SAD-1 overexpression in ASI neurons, 77 SAD kinase family, 76–77 Sah, P., 44 Sakagawa, T., 45 Salgado, J.M., 17, 175 SAP102 synaptic scaffolding proteins, 225 Scaffold proteins in postsynaptic density, 407 Scanziani, M., 39 S cerevisiae membrane trafficking study, 224–225 SCF (Skp/Cullin/F-box) complex, 81 Index SCGNs, see Presynaptic superior cervical ganglion neurons Schaffer collateral projection, 718 Schaffer collaterals, tetanic stimulation of, 766 Schielke, J.P., 43, 46 Schikorski, T., 12 Schizophrenia and mood disorders, NMDAR trafficking, 344–345 synaptic plasticity and, 272 Seal, R.P., 34 Sec5 and Sec6 mutants and neurite outgrowth, 224–225 Second mitochondria-derived activator of caspase/direct IAP-binding protein (SMAC/Diablo), 735–736 Secretory pathway, 206 and pre-assembly of postsynaptic membranes, 220 Secretory vesicles, 36 Selig, D.K., 16, 229 Semaphorins class 4, role in synapse development, 190 Sepkuty, J.P., 46 Serum-inducible kinase (SNK), 571 Serum response element (SRE)-driven gene expression, 613 Shaffer collateral-commissural synapses, 44 Shaker-type voltage-gated K+ channels, 412 Shank1b-YFP-positive excitaory synpases, 182 Shank/proSAP family, 408 scaffold protein, 407 scaffold of scaffolds, 421 homer and actin cytoskeleton interaction with, 422 multimerization of, 422 Shepherd, G.M., 8, 446 SH3/GK domain of SAP, 102, 324 Shibata, T., 43 Shimamoto, K., 39, 45 Shupliakov, O., Sidekick, immunoglobulin superfamily of proteins, 189 Signaling pathways and synaptic scaling, 541–543 Signal transduction adaptor molecule (STAM), 562 Siksou, L., Single molecule imaging in neuroscience, 395–396 797 synapses, adaptation and formation of, 397 synaptic structure stability of, 397–398 Single particle tracking experiments, 375–377 Single particle tracking (SPT) of glycine receptors, 645 Single tyrosine point mutation (Y33A) and direct axonal targeting of NgCAM, 215 Sinha, S.R., 44 SiRNA-mediated depletion of ESCRT-II, 562 Slepnev, V.I., Sliding helix model for amino acids depolarization, 148 Slit, leucine-rich repeats (LRRs), 187 Small dense core vesicles, Small ubiquitin-like modifier protein (SUMO), 579 Smith, S.J., 7, 69 Smooth endoplasmic reticulum (SER) and dendritic spines, 14, 17 and endosomal compartments, 16 SNAP-25 AZ proteins, 68 SNARE proteins, 92 SNAPs, see Soluble NSF attachment proteins SNARE-CaV2 channel complex modulation, 159 3Q/1R SNARE complex, 99 SNARE proteins binding proteins and CaV2 channels regulation, 159 complex at AZ plasma membrane, 68 dependent exocytosis during LTP, 372 function, structural requirements and specificity in synaptic vesicle fusion, 98–100 function in synaptic transmission probed by clostridial neurotoxins, 95–96 genetic analysis of, 96–98 interaction site on presynaptic Cav2 channels, 152 mediated modulation of presynaptic Ca2+ channels, biphasic model for, 157 neuronal and Ca2+-dependent synaptic vesicle fusion, 100–101 neuronal, synaptic vesicle priming, 102 regulation of presynaptic Ca2+ channels biphasic regulation of, 157 crosstalk between, 159 798 Index Syntaxin-1, anchoring and regulatory sites on, 158 vesicle tethering functional roles of, 158 role in synaptic vesicle fusion, 93–94 synaptic vesicle endocytosis and recycling, role in, 102–104 Synprint interaction and protein phosphorylation, 159–160 v-SNARE synaptobrevin point mutation, 36 Soluble NSF attachment proteins, 93 Sorra, K.E., 7, Spacek, J., 11, 13, 15, 17, 45 Spectrin-actin cytoskeleton, 274 Spike-timing dependent plasticity (STDP), 444 Spine-associated Rap-GAP, 413 Spine-associated Rap GTPase-activating protein (SPAR), 571 Spine endocytic zone, 227–228 Spine structural plasticity and endosomal recycling, 230–232 Spinophilin and neurabin cytoskeletal dynamics and spine formation, 478–479 in synaptic transmission and plasticity, 479 Src homology (SH3) domains, 114 Stargazin in LTP-induced AMPA receptor trafficking, 511 Status epilepticus state of continuous seizure activity, 717 Steiner, P., 45 Stellate cells of layer II entorhinal cortex, 718 Steric exclusion mechanisms, 260 Sterile alpha motif (SAM), 75 Stevens, C.F., 12 Stevens, J.K., 15 Steward, O., 13, 210 Stoffel, W., 46 Storm-Mathisen, J., 32, 34, 44 Striatal-Enriched Phosphatase (STEP), 342 Stroke, synaptic perspective brain ischemia, physiology and biochemistry of, 734–736 classification of, 731–732 therapeutic management of, 733 in vivo and in vitro models of, 733–734 Subsynaptic secretory pathway at neuromuscular junction (NMJ), 217 Sullivan, R., 43 Sultan, P., 12 Surface protein trafficking and fluorescence recovery, 375 Surface receptors labelling, 379 Sustained IP3- dependent calcium influxes in perisynaptic Schwann cells, 703 Svoboda, K., 24 SV proteins cycle of, 65 exocytosis, unitary active zone element for, 72 pools and neuronal cytoskeleton, 66–69 SYD-2/Liprin-α protein, 67 SYG-1 and SYG-2 transmembrane proteins, 82 Symmetric synapse, 6, 12 Synapse induction and IgG superfamily ephrins and receptors, 189 NCAM and L1-CAM, 190 NGLs and SALMS, 187–188 sidekick-1 and-2, 189 SynCAM1, 186–187 Synapse, pH fluctuations model, 663 Synapse, presynaptic component, Synapses assembly and maturation, 175 chemical, 64–65 development of, 173–174 giocentric view of, 708 induction and adhesion molecules neurodevelopmental disorders and, 185–186 neuroligins and neurexins, 177–178 excitation and inhibition, 179–180 functions of, 183–184 interactions between, 178–179 trafficking and assembly, 180–183 in vivo assessment of, 184–185 in primary synapse region (PSR) of vulval region, 571 synaptic depression during ischemia, 744 synaptic exocytosis, cardinal feature of, 78 and synaptic plasticity in dorsal horn nociceptive network, 762 heterosynaptic potentiation and, 763–765 long-term potentiation in, 765–768 rapid-onset and reversible enhancement of, 763 synaptic potentiation role in nociceptive dorsal horn neuron in pain hypersensitivity, model for, 767 Index and synaptic targeting, 218–220 synaptic vesicles of diffusion with capture in endocytic active zone, 114 diffusion in plasma membrane, 114 integrity in plasma membrane, 112–114 models of, 112 recycling of, 111–114 trafficking and maintenance of, 73–74 and transmission in dorsal horn inhibitory transmission, 761 nociceptive output, 762 primary sensory afferents and, 760–761 Synaptic adhesion-like molecules (SALMs), 187–188, 331 Synaptically-evoked Ca2+ transients, 443 Synaptic cell adhesion molecule (SynCAM1), 186–187 Synaptic Ras-GTPase activating protein (SynGAP), 330 Synaptic scaffolding molecule (S-SCAM), 330 Synaptobrevin-2 role in clathrin-mediated synaptic vesicle, 103 Synaptobrevin/VAMP, SNARE proteins, 92 Synaptogenesis in hippocampus, and putative adhesion molecules, 175 Synaptotagmin, AZ proteins, 68 Synaptotagmin I as cargo receptor for CME of SVs model, 121 Synaptotagmin and presynaptic Ca2+ channels Ca2+ channel-SNARE interaction, 155–156 exocytotic machinery and, 156–157 Syndapin/PACSIN family of proteins, 128 SynGAP protein postsynaptic scaffolding proteins, 178 scaffold protein, 407 and tSXV domain deletion, 413 Synprint peptide blocks coimmunoprecipitation of native CaV2, channels with syntaxin–1, 153 Syntaxin-13 mutants overexpression, 230 Syntaxin-1A and/or SNAP-25 co-expression with Cav2, 1/Cav2, channels, 157 Syntaxin-1, SNARE proteins, 92 Syntaxin, AZ proteins, 68 Syntenin synaptic scaffolding proteins, 186–187 799 T286 autophosphorylation, 463 Tachibana, M., 48, 420 TAG-1 adhesion molecules, 177 Takahashi, K., 35 Takamori, S., 35 Takayasu, Y., 43, 45 Takimoto, M., 26, 44 Talin-HIP1/R-Actin-Tethering C-terminal Homology (THATCH), 119 Tamir, H., 29, 38 Tanaka, K., 43, 45 Tao-Cheng, J.H., 12 Target plasma membrane SNARE (t-SNARE) proteins, 92 TARP-MAGUK interaction, 276 TARPs and AMPA receptor surface trafficking, 276–277 Taschenberger, H., 47 Temperature-sensitive Shibire mutants, 130 Tetanus neurotoxins, zinc endopeptidases, 95 Tetanus-toxin insensitive VAMP (Ti-VAMP), 97 Tetraetylammonium (TEA), sequential blockers, 302 TGN, see trans-Golgi network Theodosis, D.T., 46 Thomas, P.G., 19 Threo-betabenzyloxyaspartate (TBOA) transporter antagonists, 39 Thrombospondins (TSP)-induced synapses, 688 Tissue plasminogen activator (tPA), 733 TNF-alpha-dependent mechanism, 542 Tong, G., 42 Torpedo Ca2+ influx, 159 electric organ and vesicle, 36 electrocytes and local reorganization of microtubules, 217 Torrealba, F., Torres, G.E., 46 Transcription-dependent forms of learningrelated synaptic plasticity, 610 Transforming Growth Factor β (TGF β) signaling pathways, 611 Transient ischemic attack (TIA), 732 Transmembrane AMPA receptor regulatory proteins (TARPs), 272, 408 Trans-synaptic cell-cell adhesion molecules, 72 Tremere, L., 47 800 Index Tripartite synapse, TrkB and plasticity of mossy fiber synapses, 725 Trk receptor protein tyrosine kinases, 417 Trussell, L.O., 39 T-type Ca2+ currents, synaptic transmission at ribbon synapses, 148 Two-photon glutamate uncaging, 451 Type inositol trisphosphate receptor (IP3R), 421 Type Na+-dependent inorganic phosphate transporters, see Vesicular glutamate transporters (VGLUTs) Type I PDZ binding motif and neuroligins, 179 Tyr1472 by Fyn kinase, 330 Tyrosine phosphorylation of EphB-associated Src, 766–767 Tyrosine receptor kinase B (TrkB), 690 Tzingounis, A.V., 42, 272 Ubiquitin proteasome system (UPS) components 26S proteasome, 558 degradative pathway of, 559–561 deubiquitinating enzymes, 559 and endocytic pathway, 562–564 enzymes of, 329, 554–558 mimic ubiquitin and, 561 inhibition and rapid ischemic tolerance, 748 proteins identified in neuronal function, 557 in synapse development, 564–568 anaphase promoting complex (APC), 570–571 dendritic pruning, 571–572 in neurological disease, 579–580 Pam/Highwire/RPM-1 class of proteins, 568–570 in Parkinson’s Disease, 580–581 and postsynaptic receptor trafficking, 577–579 in postsynaptic remodeling and plasticity, 573–576 presynaptic regulation, mechanisms of, 572–573 Ueda, T., 37 Ullensvang, K., 44 UNC-104/KIF1A, kinesin motor, 84 Vacuolar-H+ATPases pump protons in synaptic vesicles, 661 VAMP2, AZ proteins, 68 VAMP2/synaptobrevin, 668 Van, Haesendonck, E., 40 Velis protein, 67, 183 Ventura, R., 19, 45 Vertebrate synapses, 69–72 Vertebrate voltage-gated K+ channel, KV1, 2, three-dimensional structure of, 148 Veruki, M.L., 47 Vesicle-associated membrane protein (VAMP2), 114, 321–322 Vesicle-associated v-SNARE protein synaptobrevin (VAMP), 151 Vesicle-containing axonal boutons, Vesicle trafficking and myosin motors, 224 Vesicular glutamate transporters (VGLUTs), 31–33 characteristics of, 29–30 distribution and synaptic role, 31–33 transporters of, 30–31 Vesicular neurotransmitter transport, bioenergetics of, 27 Vesicular stomatitis viral glycoprotein (VSVG-ts), 211 2-and 4-Vessel occlusion, 733 VGLUT1-independent transmission in hippocampus, 32 VGLUT3 and synaptic plasticity, 32 Viruses intracellular trafficking, 377 Visinin-like protein-2 (VILIP-2), 163–164 VMATs turnover for serotonin, 31 Voltage-gated calcium channels (VGCC), 67 Volterra, A., Volume-sensitive ion channels in astrocytes, 704 Von Gersdorff, H., 47 VSVG and LDL receptor (basolateral/somatodendritic), 215 Wada, K., 26, 44, 47 Wadiche, J.I., 41, 42, 44, 47 Wallerian axonal degeneration, 568 Walther, D.J., 35 Wang, Y., 46, 74, 78 Warnick, J.E., 42 Warr, O., 40 Index Watanabe, M., 43–45, 47, 30, 43, 44, 45, 47 Watase, K., 26, 44, 47 Watford, M., 25 Watkins, A.M., 43 Webster, H.D., 12 Weinberg, R.J., 76 Weinstein, L.A., Welker, E., 45 Wiessner, M., 43 Wild type Drosophila neuromuscular junction, 37 Wild type Drp1 overexpression, 214 Wild-type Rnf6 overexpression in axon growth, 567 Willardiine agonists and GluR5, GluR6 subtype kainate receptors, 260 Wilson, C.J., Wingless-Int (wnt) signaling pathways, 611 Winter, S., 35 Witcher, M.R., 19 Wnt receptor lin-17/Frizzled, 83 Woolley, C.S., 17 801 Wu, D., 46 WXXF-acidic α-ear-binding motif in the NECAP proteins, 134 Xenopus nerve-muscle co-cultures, CaV2, channels, 156 optic tectum neurons, 338–339 Xu-Friedman, M.A., Yamada, K., 43–44 Yanagihara, D., 47 Yankova, M., Yasuda-Kamatani, Y., 39 Yeast ESCRT-III complex, 564 YEKL internalization motif on NR2B subunit, 328 Yi, E., 45 Zippering SNARE complexes, 93 Ziv, N.E., Zn2+ accelerated receptor desensitization, 303 ZNRF family of RING domain E3 ligases, 573 ... deciphering the structural and functional organization of the synapse We have assembled leaders in the field of synapse biology to describe and distill the wonders and mysteries of the synapse This.. .STRUCTURAL AND FUNCTIONAL ORGANIZATION OF THE SYNAPSE STRUCTURAL AND FUNCTIONAL ORGANIZATION OF THE SYNAPSE Edited by Johannes W Hell University of Iowa Iowa City, IA, USA and Michael... must occur within the tiny space of the synapse, the precise molecular organization of proteins, lipids, and membranes at the synapse is paramount Given the central role of the synapse in neuronal