The Endomembrane System and Proteins

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The Endomembrane System and Proteins The Endomembrane System and Proteins Bởi: OpenStaxCollege The endomembrane system (endo = “within”) is a group of membranes and organelles ([link]) in eukaryotic cells that works together to modify, package, and transport lipids and proteins It includes the nuclear envelope, lysosomes, and vesicles, which we’ve already mentioned, and the endoplasmic reticulum and Golgi apparatus, which we will cover shortly Although not technically within the cell, the plasma membrane is included in the endomembrane system because, as you will see, it interacts with the other endomembranous organelles The endomembrane system does not include the membranes of either mitochondria or chloroplasts Art Connection 1/9 The Endomembrane System and Proteins "Membrane and secretory proteins are synthesized in the rough endoplasmic reticulum (RER) The RER also sometimes modifies proteins In this illustration, a (green) integral membrane protein in the ER is modified by attachment of a (purple) carbohydrate Vesicles with the integral protein bud from the ER and fuse with the cis face of the Golgi apparatus As the protein passes along the Golgi’s cisternae, it is further modified by the addition of more carbohydrates After its synthesis is complete, it exits as integral membrane protein of the vesicle that bud from the Golgi’s trans face and when the vesicle fuses with the cell membrane the protein becomes integral portion of that cell membrane (credit: modification of work by Magnus Manske) If a peripheral membrane protein were synthesized in the lumen (inside) of the ER, would it end up on the inside or outside of the plasma membrane? The Endoplasmic Reticulum The endoplasmic reticulum (ER) ([link]) is a series of interconnected membranous sacs and tubules that collectively modifies proteins and synthesizes lipids However, these two functions are performed in separate areas of the ER: the rough ER and the smooth ER, respectively 2/9 The Endomembrane System and Proteins The hollow portion of the ER tubules is called the lumen or cisternal space The membrane of the ER, which is a phospholipid bilayer embedded with proteins, is continuous with the nuclear envelope Rough ER The rough endoplasmic reticulum (RER) is so named because the ribosomes attached to its cytoplasmic surface give it a studded appearance when viewed through an electron microscope ([link]) This transmission electron micrograph shows the rough endoplasmic reticulum and other organelles in a pancreatic cell (credit: modification of work by Louisa Howard) Ribosomes transfer their newly synthesized proteins into the lumen of the RER where they undergo structural modifications, such as folding or the acquisition of side chains These modified proteins will be incorporated into cellular membranes—the membrane of the ER or those of other organelles—or secreted from the cell (such as protein hormones, enzymes) The RER also makes phospholipids for cellular membranes If the phospholipids or modified proteins are not destined to stay in the RER, they will reach their destinations via transport vesicles that bud from the RER’s membrane ([link]) Since the RER is engaged in modifying proteins (such as enzymes, for example) that will be secreted from the cell, you would be correct in assuming that the RER is abundant in cells that secrete proteins This is the case with cells of the liver, for example Smooth ER The smooth endoplasmic reticulum (SER) is continuous with the RER but has few or no ribosomes on its cytoplasmic surface ([link]) Functions of the SER include synthesis of carbohydrates, lipids, and steroid hormones; detoxification of medications and poisons; and storage of calcium ions 3/9 The Endomembrane System and Proteins In muscle cells, a specialized SER called the sarcoplasmic reticulum is responsible for storage of the calcium ions that are needed to trigger the coordinated contractions of the muscle cells Link to Learning You can watch an excellent animation of the endomembrane system here At the end of the animation, there is a short self-assessment Career Connection CardiologistHeart disease is the leading cause of death in the United States This is primarily due to our sedentary lifestyle and our high trans-fat diets Heart failure is just one of many disabling heart conditions Heart failure does not mean that the heart has stopped working Rather, it means that the heart can’t pump with sufficient force to transport oxygenated blood to all the vital organs Left untreated, heart failure can lead to kidney failure and failure of other organs The wall of the heart is composed of cardiac muscle tissue Heart failure occurs when the endoplasmic reticula of cardiac muscle cells not function properly As a result, an insufficient number of calcium ions are available to trigger a sufficient contractile force Cardiologists (cardi- = “heart”; -ologist = “one who studies”) are doctors who specialize in treating heart diseases, including heart ...A new siglec family member, siglec-10, is expressed in cells of the immune system and has signaling properties similar to CD33 Gena Whitney 1 , Shulin Wang 1 , Han Chang 2 , Ke-Yi Cheng 1 , Pin Lu 1 , Xia D. Zhou 1 , Wen-Pin Yang 2 , Murray McKinnon 1 and Malinda Longphre 1 1 Inflammation and Pulmonary Drug Discovery Department, and 2 Applied Genomics Department, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA The siglecs (sialic acid-binding Ig-like lectins) are a distinct subset of the Ig superfamily with adhesion-molecule-like structure. We describe here a novel member of the siglec protein family that shares a similar structure including five Ig-like domains, a transmembrane domain, and a cyto- plasmic tail containing two ITIM-signaling motifs. Siglec- 10 was identified through database mining of an asthmatic eosinophil EST library. Using the Stanford G3 radiation hybrid panel we were able to localize the genomic sequence of siglec-10 within the cluster of genes on chromosome 19q13.3-4 that encode other siglec family members. We have demonstrated that siglec-10 is an immune system- restricted membrane-bound protein that is highly expressed in peripheral blood leukocytes as demonstrated by Northern, RT-PCR and flow cytometry. Binding assays determined that the extracellular domain of siglec-10 was capable of binding to peripheral blood leukocytes. The cytoplasmic tail of siglec-10 contains four tyrosines, two of which are embedded in ITIM-signaling motifs (Y597 and Y667) and are likely involved in intracellular signaling. The ability of tyrosine kinases to phosphorylate the cytoplasmic tyrosines was evaluated by kinase assay using wild-type siglec-10 cytoplasmic domain and Y!F mutants. The majority of the phosphorylation could be attributed to Y597 and Y667. Further experiments with cell extracts suggest that Src homology region 2 domain-containing protein tyrosine phosphatase (SHP)-1 interacts with Y667 and SHP-2 interacts with Y667 in addition to another tyrosine. This is very similar to CD33, which also binds the phosphatases SHP-1 and SHP-2, therefore siglec-10, as CD33, may be characterized as an inhibitory receptor. Keywords: sialoadhesin; CD33; inhibitory receptor; phos- phatase; siglec. A recently defined group of immunoglobulin superfamily proteins expressed on a variety of cell types have been described as having binding properties that may mediate cell adhesion and cell signaling through recognition of sialyated cell surface glycans [1,2]. This protein family was recently termed siglec for sialic acid-binding Ig-like lectins and is comprised of sialoadhesin (siglec-1) [3], CD22 (siglec-2) [4], CD33 (siglec-3) [5], myelin-associated glycoprotein (MAG, siglec-4a) [6], Schwann cell myelin protein (SMP, siglec-4b) [4], OB-BP2 (siglec-5) [7], OB-BP1 (siglec-6) [8], siglec-7 [9], siglec-8 [10], and siglec-9 [11,12]. Although expression of certain siglecs (e.g. CD33) has long been observed and utilized for diagnosis of some malignant disorders [13], the precise biological functions of the siglec protein family are not well understood. However, because of their structure and expression patterns, siglec proteins are hypothesized to be involved in diverse biological processes such as hematopoiesis, neuronal development and immunity [2]. A trait shared by many of EEccoonnoommiiccss,, tthhee EEnntteerrpprriissee SSyysstteemm,, aanndd FFiinnaannccee February 2002 The University of the State of New York • The State Education Department Albany, NY 12234 www.nysed.gov THE UNIVERSITY OF THE STATE OF NEW YORK Regents of The University C ARL T. HAYDEN, Chancellor, A.B., J.D. Elmira A DELAIDE L. SANFORD, Vice Chancellor, B.A., M.A., P.D. Hollis D IANE O’NEILL MCGIVERN, B.S.N., M.A., Ph.D. Staten Island S AUL B. COHEN, B.A., M.A., Ph.D. New Rochelle J AMES C. DAWSON, A.A., B.A., M.S., Ph.D. Peru R OBERT M. BENNETT, B.A., M.S. Tonawanda R OBERT M. JOHNSON, B.S., J.D. Huntington A NTHONY S. BOTTAR, B.A., J.D. North Syracuse M ERRYL H. TISCH, B.A., M.A. New York E NA L. FARLEY, B.A., M.A., Ph.D. Brockport G ERALDINE D. CHAPEY, B.A., M.A., Ed.D Belle Harbor A RNOLD B. GARDNER, B.A., LL.B Buffalo C HARLOTTE K. FRANK, B.B.A., M.S.Ed., Ph.D. New York H ARRY PHILLIPS, 3 rd , B.A., M.S.F.S. Hartsdale J OSEPH E. BOWMAN, JR., B.A., M.L.S., M.A., M.Ed., Ed.D Albany L ORRAINE A. CORTÉ S-VÁZQUEZ, B.A., M.P.A Bronx President of The University and Commissioner of Education R ICHARD P. MILLS Chief Operating Officer RICHARD H. CATE Deputy Commissioner for Elementary, Middle, Secondary, and Continuing Education J AMES A. 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Inquiries concerning this policy of nondiscrimination should be directed to the Department’s Office for Diversity, Ethics, and Access, Room 530, Education Building, Albany, NY 12234. ii FF FF oo oo rr rr ee ee ww ww oo oo rr rr dd dd T his core curriculum for economics, the enterprise system, and finance supports the State Education Department’s efforts to raise standards in social studies by focusing on Standard 4: Economics, in the Learning Standards for Social Studies. This core curriculum reinforces the key ideas and performance indi- cators for this standard and describes what students should know and be able to do in their study of economics and economic decision making. It outlines the content, concepts, and skills that students should understand and apply throughout their lives. Decisions about what information to include reflect the collaborative efforts of leaders in social studies education, business, finance, and economics education. These decisions were based on the need to pro- vide students with the economic knowledge and skills that will enable them to function as informed and economi- cally literate citizens in our democratic society and in the global marketplace. This new core curriculum includes information about business, entrepreneurship, the enterprise system, finance, and personal finance, in addition to economic theory. Economics, the Enterprise System, and Finance is intended to be used to meet the curriculum mandate of the Board of Regents that requires all students to complete a half-unit course of study in economics or its equivalent as part of their four-unit social studies requirement. Equivalent courses in economics must address Social Studies Learning Standard 4: Economics, specifically the key ideas and performance indicators that define this Genome Biology 2005, 6:211 comment reviews reports deposited research interactions information refereed research Minireview Tumor microenvironments, the immune system and cancer survival Robert L Strausberg Address: J. Craig Venter Institute, 9,704 Medical Center Drive, Rockville, MD 20850, USA. E-mail: RLS@venterinstitute.org Abstract The study of cancer immunology has recently been reinvigorated by the application of new research tools and technologies, as well as by refined bioinformatics methods for interpretation of complex datasets. Recent microarray analyses of lymphomas suggest that the prognosis of cancer patients is related to an interplay between cancer cells and their microenvironment, including the immune response. Published: 1 March 2005 Genome Biology 2005, 6:211 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2005/6/3/211 © 2005 BioMed Central Ltd That the immune system plays an important role in the regu- lation and outcome of cancer has been an intriguing concept for almost a century. As discussed by Dunn et al. [1,2], although many observations supported the notion that the ability of cancer to escape the tumor-controlling features of the immune system can be considered a hallmark of cancer, for many years the scientific evidence was conflicting and consensus did not emerge. More recently, however, advances in approaches that perturb specific gene functions in well-defined mouse models of cancer have convincingly demonstrated the importance of the interface between cancer and the immune system [2]. Together with a large body of evidence from human cancers, these advances have generated renewed interest in understanding the role of the host inflammatory response in cancer and in using that knowledge towards the development of new approaches to cancer immunotherapy and vaccination [3-10]. The recently reported results of two groups [11,12] give new insights into the factors that affect survival of patients with lymphomas, including the importance of the immune system. Initially, the study of cancer immunobiology was framed within the context of ‘immunosurveillance’ [13], with focus on the role of the immune system in recognizing and inhibit- ing cancer growth. More recently, it has been recognized that the interrelationship between cancer and the immune system is highly complex and can take very different paths - for instance, from suppression of tumor growth by the immune system or enhancement of tumor progression through the selection of cells so that they lack signals recog- nized by the immune system. Given this complex biology, it has been suggested that the term immunosurveillance [13] be replaced with the more comprehensive term ‘immuno- editing’, encompassing three phases: elimination, equilib- rium, and escape [1] (Figure 1). In the elimination phase, which is perhaps the most similar to the original concept of immunosurveillance, the immune system attempts to eradi- cate the cancer. If this process is unsuccessful, the cancer and the immune system achieve a balance, referred to here as equilibrium, in which the immune system is able to contain but not eliminate the cancer. During the equilibrium phase the cancer is under constant pressure from the immune system but can also undergo genetic changes that can lead to increased immune resistance. If, following many rounds of selection and genetic change, the cancer cells become resistant to immune attack, the escape phase com- mences, in which the cancer cells are now free to progress, even in the presence of an intact immune system. Microarrays and cancer immunology Out of this background have emerged new technological advances, including microarrays, which provide the oppor- tunity comprehensively to assess gene expression in tumors, their component cells, and their microenvironment. Among the important advances that have derived from these tech- nologies is the molecular classification [...]... later, the Federal Reserve and many other central banks around the world continue to ignore the complex structures of modern financial markets and officially produce and supply lowquality monetary statistics, using the severely flawed simple-sum method of aggregation, inconsistent with the relevant aggregation and index-number theory In doing so, they misled themselves, as well as households and firms,... in the system However, as the Fed is searching for new tools to steer the US economy in an environment with the federal funds rate at the zero lower bound and the level of excess reserves in the trillions of dollars (see again the preceding figure), no one is sure how this will unfold! Recently, in the aftermath of the subprime financial crisis and the Great Recession, policy makers, the media, and. .. associated with the Barnett critique,” to use the phrase coined by Alec Chrystal and Ronald MacDonald (1994) Barnett (1980a) argued that the monetary aggregates used by the Federal Reserve are problematic, being inconsistent with neoclassical microeconomic theory and therefore should be abandoned These monetary aggregates are simple-sum indexes, in which all financial assets are assigned a constant and equal... interest rate from (the usual) 50 basis points to 25 basis points (a band with rates between ¼ and ½ percent) and instead of targeting the overnight rate at the midpoint of the band (as it does during normal times), it targeted the overnight rate at the bottom of the operating band On June 1, 2010, the Bank of Canada re-established the normal operating band of 50 basis points for the overnight interest... high-quality monetary statistics In this excellent and research-based book, William A Barnett departs from the view that the financial crisis and the Great Recession were caused by the failure of mainstream economic theory He argues the converse: that there was too little use of the relevant economic theory, especially of the literature on economic measurement and on nonlinear dynamics Barnett argues that... why an expansionary monetary policy could have prevented the sharp decline in output in the United States during the Great Depression of the 1930s, why it would have helped the Japanese economy when nominal interest rates fell to near zero in the late 1990s, and why it could help the United States accelerate the economic recovery in the aftermath of the Great Recession However, the collapse of stable... “American Monetary Policy: Fed under Fire” and The Politics of the Fed: Bernanke in the Crosshairs.” If it does, it may create even bigger headaches for the Fed In particular, a by-product of the Fed’s quantitative easing is the creation of a large quantity of excess reserves, as can be seen in the figure above (where the shaded area represents the Great Recession) During normal times, when the opportunity... regarding the levels of systemic risk in the economy Also, unfortunately, thirty years later, the Federal Reserve System does not even include an autonomous data bureau staffed with experts in index-number and aggregation theory, such as the Bureau of Labor Statistics, within the Department of Labor, or the Bureau of Economic Analysis, within the Department of Commerce, to produce and supply high-quality monetary. .. specialized and to make the kind of confident quantitative claims that often emerge from the core On ... proteins and synthesizes lipids However, these two functions are performed in separate areas of the ER: the rough ER and the smooth ER, respectively 2/9 The Endomembrane System and Proteins The. .. with it, and empty their contents into the lumen of the Golgi apparatus As the proteins and lipids travel through the Golgi, they undergo further modifications that allow them to be sorted The most.. .The Endomembrane System and Proteins "Membrane and secretory proteins are synthesized in the rough endoplasmic reticulum (RER) The RER also sometimes modifies proteins In this