Synaptic vesicles and exocytosis.

Neurons transmit information by releasing neurotransmitters from presynaptic nerve endings, In the resting stage , transmitters are stored in small organelles of uniform size and shape , the synaptic vesicles . When an action potential arrives in the nerve terminal , the membrane depolarizes and voltage-gated Ca2+ channels open . The resulting Ca2+ influx triggers exocytosis of synaptic vesicles , resulting in the release of neurotransmitter. The synaptic vesicle membrane is rapidly retrieved by endocytosis and reutilized for the formation of synaptic vesicles. These vesicles are reloaded with transmitter for another round of exocytosis . This cycle is repeated many times and can be studied in nerve terminals that have no connection with the neuronal cell body . Thus , the presynaptic compartment consists of an autonomous unit that contains all components required for repetitive exocytosis and membrane recycling . In contrast, release of neuropeptides involves large dense core vesicles that follow a different route; they will not be considered in this discussion (for review, see Thureson-Klein & Klein 1990) . Although the principles o f synaptic vesicle membrane traffic were worked out many years ago (reviewed by Ceccarelli & Hurlbut 1980) , it remains a major challenge to define the molecular events underlying the individual

[1]  T. Südhof,et al.  Cellubrevin is a ubiquitous tetanus-toxin substrate homologous to a putative synaptic vesicle fusion protein , 1993, Nature.

[2]  T. Südhof,et al.  Synaptic Vesicle Traffic: Rush Hour in the Nerve Terminal , 1993, Journal of neurochemistry.

[3]  P. De Camilli,et al.  Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. , 1993, The New England journal of medicine.

[4]  S. Morris,et al.  Clathrin assembly protein AP180: primary structure, domain organization and identification of a clathrin binding site. , 1993, The EMBO journal.

[5]  R. Scheller,et al.  A role for synaptotagmin (p65) in regulated exocytosis , 1993, Cell.

[6]  T. Stevens,et al.  Isolation of vacuolar membrane H(+)-ATPase-deficient yeast mutants; the VMA5 and VMA4 genes are essential for assembly and activity of the vacuolar H(+)-ATPase. , 1993, The Journal of biological chemistry.

[7]  M. Takahashi,et al.  HPC-1 is associated with synaptotagmin and omega-conotoxin receptor. , 1992, The Journal of biological chemistry.

[8]  J. H. Chou,et al.  Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis. , 1992, Biochemical and biophysical research communications.

[9]  N. Hirokawa,et al.  The phosphorylation of kinesin regulates its binding to synaptic vesicles. , 1992, The Journal of biological chemistry.

[10]  F. Benfenati,et al.  Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin , 1992, Nature.

[11]  Y. Nishizuka Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. , 1992, Science.

[12]  M. Adams,et al.  Calcium channels coupled to glutamate release identified by omega-Aga-IVA. , 1992, Science.

[13]  Fabio Benfenati,et al.  Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I , 1992, Nature.

[14]  M. Feany,et al.  The synaptic vesicle protein SV2 is a novel type of transmembrane transporter , 1992, Cell.

[15]  P. Maycox,et al.  Clathrin-coated vesicles in nervous tissue are involved primarily in synaptic vesicle recycling , 1992, The Journal of cell biology.

[16]  R. Scheller,et al.  SV2, a brain synaptic vesicle protein homologous to bacterial transporters. , 1992, Science.

[17]  D. Eisenberg,et al.  A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter , 1992, Cell.

[18]  R. Holz,et al.  Kinetic analysis of secretion from permeabilized adrenal chromaffin cells reveals distinct components. , 1992, The Journal of biological chemistry.

[19]  E. Ungewickell,et al.  Clathrin-associated proteins of bovine brain coated vesicles. An analysis of their number and assembly-promoting activity. , 1992, The Journal of biological chemistry.

[20]  E. Wright,et al.  Sodium cotransport proteins. , 1992, Current opinion in cell biology.

[21]  D. Botstein,et al.  The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase. , 1992, The Journal of biological chemistry.

[22]  R. Scheller,et al.  Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. , 1992, Science.

[23]  T. Südhof,et al.  Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin. , 1992, Science.

[24]  M. Kilimann,et al.  Amphiphysin, a novel protein associated with synaptic vesicles. , 1992, The EMBO journal.

[25]  H. Lodish,et al.  Cloning of a Rab3 isotype predominantly expressed in adipocytes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[26]  S. Zhou,et al.  Characterization of a novel synapse-specific protein. I. Developmental expression and cellular localization of the F1-20 protein and mRNA , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  R. Kelly,et al.  Specific association of the proto-oncogene product pp60c-src with an intracellular organelle, the PC12 synaptic vesicle , 1992, The Journal of cell biology.

[28]  K. Akagawa,et al.  Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. , 1992, The Journal of biological chemistry.

[29]  M. Wigler,et al.  SNC1, a yeast homolog of the synaptic vesicle-associated membrane protein/synaptobrevin gene family: genetic interactions with the RAS and CAP genes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[30]  P. De Camilli,et al.  Exo-endocytotic recycling of synaptic vesicles in developing processes of cultured hippocampal neurons , 1992, The Journal of cell biology.

[31]  M. Takeichi,et al.  Epimorphin: A mesenchymal protein essential for epithelial morphogenesis , 1992, Cell.

[32]  R Llinás,et al.  Microdomains of high calcium concentration in a presynaptic terminal. , 1992, Science.

[33]  Q. Al-Awqati,et al.  A ubiquitous 64-kDa protein is a component of a chloride channel of plasma and intracellular membranes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[34]  P. Greengard,et al.  Structure and function of the synapsins. , 1992, The Journal of biological chemistry.

[35]  Dennis Brown,et al.  Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56-kilodalton subunit in renal intercalated cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Lévêque,et al.  The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  R. Staden,et al.  The C. elegans genome sequencing project: a beginning , 1992, Nature.

[38]  P. Greengard,et al.  Interaction of free and synaptic vesicle-bound synapsin I with F-actin , 1992, Neuron.

[39]  W. Betz,et al.  Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. , 1992, Science.

[40]  R. Schekman,et al.  Vesicle-mediated protein sorting. , 1992, Annual review of biochemistry.

[41]  C. Kumamoto,et al.  A single gene encodes the catalytic "A" subunit of the bovine vacuolar H(+)-ATPase. , 1991, The Journal of biological chemistry.

[42]  R. Kelly,et al.  Molecular architecture of the nerve terminal , 1991, Current Opinion in Neurobiology.

[43]  R. Scheller,et al.  A synaptic vesicle specific GTP-binding protein from ray electric organ. , 1991, Brain research. Molecular brain research.

[44]  J. Hell,et al.  GABA and glycine in synaptic vesicles: storage and transport characteristics , 1991, Neuron.

[45]  I. Zagon,et al.  Synapsin I-mediated interaction of brain spectrin with synaptic vesicles , 1991, The Journal of cell biology.

[46]  P. Johnston,et al.  rab3A attachment to the synaptic vesicle membrane mediated by a conserved polyisoprenylated carboxy-terminal sequence , 1991, Neuron.

[47]  J. D. Clark,et al.  A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP , 1991, Cell.

[48]  D. Hall,et al.  Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans , 1991, Cell.

[49]  D. Gallwitz,et al.  Identification and structure of four yeast genes (SLY) that are able to suppress the functional loss of YPT1, a member of the RAS superfamily , 1991, Molecular and cellular biology.

[50]  T. Südhof,et al.  Domain structure of synaptotagmin (p65) , 1991, The Journal of biological chemistry.

[51]  M Linial,et al.  Cellular and molecular biology of the presynaptic nerve terminal. , 1991, Annual review of neuroscience.

[52]  P. Parham,et al.  Clathrin light chains: arrays of protein motifs that regulate coated-vesicle dynamics. , 1991, Trends in biochemical sciences.

[53]  T. Noumi,et al.  Molecular cloning of cDNA encoding the C subunit of H(+)-ATPase from bovine chromaffin granules. , 1990, The Journal of biological chemistry.

[54]  T. Rausch,et al.  An mRNA from human brain encodes an isoform of the B subunit of the vacuolar H(+)-ATPase. , 1990, The Journal of biological chemistry.

[55]  T. Südhof,et al.  Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2. , 1990, The Journal of biological chemistry.

[56]  B. Marquèze-Pouey,et al.  Synaptoporin, a novel putative channel protein of synaptic vesicles , 1990, Neuron.

[57]  W. Almers,et al.  Transmitter release from synapses: Does a preassembled fusion pore initiate exocytosis? , 1990, Neuron.

[58]  T. Südhof,et al.  Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C , 1990, Nature.

[59]  R. Molday,et al.  Molecular cloning, primary structure, and orientation of the vertebrate photoreceptor cell protein peripherin in the rod outer segment disk membrane. , 1990, Biochemistry.

[60]  R. Hirata,et al.  Molecular structure of a gene, VMA1, encoding the catalytic subunit of H(+)-translocating adenosine triphosphatase from vacuolar membranes of Saccharomyces cerevisiae. , 1990, The Journal of biological chemistry.

[61]  T. Südhof,et al.  rab3 is a small GTP-binding protein exclusively localized to synaptic vesicles. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[62]  J. Rossier,et al.  A 15 kDa proteolipid found in mediatophore preparations from Torpedo electric organ presents high sequence homology with the bovine chromaffin granule protonophore , 1990, FEBS letters.

[63]  M. Linial,et al.  Torpedo synaptophysin: evolution of a synaptic vesicle protein , 1990, Brain Research.

[64]  H. Arai,et al.  Dissociation, cross-linking, and glycosylation of the coated vesicle proton pump. , 1990, The Journal of biological chemistry.

[65]  K. Miller,et al.  Multiple GTP-binding proteins from cholinergic synaptic vesicles , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[66]  N. Hirokawa,et al.  Conformational change and localization of calpactin I complex involved in exocytosis as revealed by quick-freeze, deep-etch electron microscopy and immunocytochemistry. , 1990 .

[67]  Å. Thureson-Klein,et al.  Exocytosis from neuronal large dense-cored vesicles. , 1990, International review of cytology.

[68]  M. Robinson,et al.  Clathrin, adaptors, and sorting. , 1990, Annual review of cell biology.

[69]  E. Neher,et al.  The patch-clamp technique in the study of secretion , 1989, Trends in Neurosciences.

[70]  J. Heuser,et al.  The role of coated vesicles in recycling of synaptic vesicle membrane. , 1989, Cell biology international reports.

[71]  X. Xie,et al.  Isolation and reconstitution of the chloride transporter of clathrin-coated vesicles. , 1989, The Journal of biological chemistry.

[72]  D. K. Stone,et al.  Vacuolar proton pumps , 1989, Journal of bioenergetics and biomembranes.

[73]  P. De Camilli,et al.  Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins. , 1989, Science.

[74]  E. Floor,et al.  Synaptic vesicle ceramide kinase. A calcium-stimulated lipid kinase that co-purifies with brain synaptic vesicles. , 1989, The Journal of biological chemistry.

[75]  X. Xie,et al.  Human endomembrane H+ pump strongly resembles the ATP-synthetase of Archaebacteria. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[76]  P. Chardin,et al.  The human Rab genes encode a family of GTP-binding proteins related to yeast YPT1 and SEC4 products involved in secretion. , 1989, The Journal of biological chemistry.

[77]  R. Scheller,et al.  Two vesicle-associated membrane protein genes are differentially expressed in the rat central nervous system. , 1989, The Journal of biological chemistry.

[78]  M. Forgac Structure and function of vacuolar class of ATP-driven proton pumps. , 1989, Physiological reviews.

[79]  P. Haydon,et al.  Formation and modulation of chemical connections: Evoked acetylcholine release from growth cones and neurites of specific identified neurons , 1989, Neuron.

[80]  N. Nelson,et al.  The progenitor of ATP synthases was closely related to the current vacuolar H+‐ATPase , 1989, FEBS letters.

[81]  N. Nelson,et al.  A conserved gene encoding the 57-kDa subunit of the yeast vacuolar H+-ATPase. , 1989, The Journal of biological chemistry.

[82]  J. Meldolesi,et al.  α-Latrotoxin and related toxins , 1989 .

[83]  R. Doms,et al.  Protein-mediated membrane fusion. , 1989, Annual review of biophysics and biophysical chemistry.

[84]  Stephen J. Smith,et al.  Calcium ions, active zones and synaptic transmitter release , 1988, Trends in Neurosciences.

[85]  B. F. Ouellette,et al.  cDNA sequence and homologies of the "57-kDa" nucleotide-binding subunit of the vacuolar ATPase from Arabidopsis. , 1988, The Journal of biological chemistry.

[86]  E. Bamberg,et al.  Identification of synaptophysin as a hexameric channel protein of the synaptic vesicle membrane. , 1988, Science.

[87]  E. J. Bowman,et al.  Isolation of genes encoding the Neurospora vacuolar ATPase. Analysis of vma-1 encoding the 67-kDa subunit reveals homology to other ATPases. , 1988, The Journal of biological chemistry.

[88]  J. Hell,et al.  Uptake of GABA by rat brain synaptic vesicles isolated by a new procedure. , 1988, The EMBO journal.

[89]  T. Südhof,et al.  The structure of cytochrome b561, a secretory vesicle‐specific electron transport protein. , 1988, The EMBO journal.

[90]  Irving S. Sigal,et al.  Cloning of bovine GAP and its interaction with oncogenic ras p21 , 1988, Nature.

[91]  Y. Takai,et al.  Nucleotide and deduced amino acid sequences of a GTP-binding protein family with molecular weights of 25,000 from bovine brain. , 1988, The Journal of biological chemistry.

[92]  M. Mandel,et al.  cDNA sequence encoding the 16-kDa proteolipid of chromaffin granules implies gene duplication in the evolution of H+-ATPases. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[93]  B. Sakmann,et al.  Ion channels in synaptic vesicles from Torpedo electric organ. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[94]  V. Sukhatme,et al.  Isolation and sequence of a cDNA clone encoding the 31-kDa subunit of bovine kidney vacuolar H+-ATPase. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[95]  F. Fonnum,et al.  Uptake of γ‐Aminobutyric Acid by a Synaptic Vesicle Fraction Isolated from Rat Brain , 1988 .

[96]  R. Kriz,et al.  Sequence similarity of phospholipase C with the non-catalytic region of src , 1988, Nature.

[97]  P. Chardin,et al.  Complete coding sequences of the ras related rab 3 and 4 cDNAs. , 1988, Nucleic acids research.

[98]  P. Greengard,et al.  Protein tyrosine phosphorylation in synaptic vesicles. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[99]  R. Johnson,et al.  Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport. , 1988, Physiological reviews.

[100]  P. Greengard,et al.  A synaptic vesicle protein with a novel cytoplasmic domain and four transmembrane regions. , 1987, Science.

[101]  P. Kaiser,et al.  Synaptophysin: molecular organization and mRNA expression as determined from cloned cDNA. , 1987, The EMBO journal.

[102]  S. Parsons,et al.  The vesicular acetylcholine transport system , 1987, Trends in Neurosciences.

[103]  K. Obata,et al.  Four synaptic vesicle-specific proteins: identification by monoclonal antibodies and distribution in the nervous tissue and the adrenal medulla , 1987, Brain Research.

[104]  S. Schuldiner,et al.  Mechanism of Transport and Storage of Neurotransmitter , 1987 .

[105]  B. Wiedenmann,et al.  Molecular characterization of synaptophysin, a major calcium‐binding protein of the synaptic vesicle membrane. , 1986, The EMBO journal.

[106]  A. Scarpa,et al.  Evidence for an ascorbate shuttle for the transfer of reducing equivalents across chromaffin granule membranes. , 1986, The Journal of biological chemistry.

[107]  R. Kelly,et al.  Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells , 1985, The Journal of cell biology.

[108]  R. Kelly,et al.  Calmodulin is tightly associated with synaptic vesicles independent of calcium. , 1984, The Journal of biological chemistry.

[109]  C. Sander,et al.  A yeast gene encoding a protein homologous to the human c-has/bas proto-oncogene product , 1983, Nature.

[110]  Mu-ming Poo,et al.  Spontaneous release of transmitter from growth cones of embryonic neurones , 1983, Nature.

[111]  W. P. Hurlbut,et al.  Vesicle hypothesis of the release of quanta of acetylcholine. , 1980, Physiological reviews.

[112]  V. Tennyson The Fine Structure of the Nervous System. , 1970 .

[113]  K. Titani,et al.  THE STRUCTURE OF CYTOCHROME C , 1958 .