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Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission
Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (22), p.10727-10731 |
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creator | Broadie, K. (University of Cambridge, Cambridge, United Kingdom) Bellen, H.J DiAntonio, A Littleton, J.T Schwarz, T.L |
description | Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence of synaptotagmin, synaptic transmission is dramatically impaired but is not abolished. In null mutants, evoked vesicle release is decreased by a factor of 10. Moreover, the fidelity of excitation-secretion coupling is impaired so that a given stimulus generates a more variable amount of secretion. However, this residual evoked release shows Ca2+-dependence similar to normal release, suggesting either that synaptotagmin is not the Ca2+ sensor or that a second, independent Ca2+ sensor exists. While evoked transmission is suppressed, the rate of spontaneous vesicle fusion is increased by a factor of 5. We conclude that synaptotagmin is not an absolutely essential component of the Ca2+-dependent secretion pathway in synaptic transmission but is necessary for normal levels of transmission. Our data support a model in which synaptotagmin functions as a negative regulator of spontaneous vesicle fusion and acts to increase the efficiency of excitation-secretion coupling during synaptic transmission |
doi_str_mv | 10.1073/pnas.91.22.10727 |
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(University of Cambridge, Cambridge, United Kingdom) ; Bellen, H.J ; DiAntonio, A ; Littleton, J.T ; Schwarz, T.L</creator><creatorcontrib>Broadie, K. (University of Cambridge, Cambridge, United Kingdom) ; Bellen, H.J ; DiAntonio, A ; Littleton, J.T ; Schwarz, T.L</creatorcontrib><description>Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence of synaptotagmin, synaptic transmission is dramatically impaired but is not abolished. In null mutants, evoked vesicle release is decreased by a factor of 10. Moreover, the fidelity of excitation-secretion coupling is impaired so that a given stimulus generates a more variable amount of secretion. However, this residual evoked release shows Ca2+-dependence similar to normal release, suggesting either that synaptotagmin is not the Ca2+ sensor or that a second, independent Ca2+ sensor exists. While evoked transmission is suppressed, the rate of spontaneous vesicle fusion is increased by a factor of 5. We conclude that synaptotagmin is not an absolutely essential component of the Ca2+-dependent secretion pathway in synaptic transmission but is necessary for normal levels of transmission. Our data support a model in which synaptotagmin functions as a negative regulator of spontaneous vesicle fusion and acts to increase the efficiency of excitation-secretion coupling during synaptic transmission</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.91.22.10727</identifier><identifier>PMID: 7938019</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Animals ; Biochemistry ; CALCIO ; CALCIUM ; Calcium - metabolism ; Calcium-Binding Proteins ; CATION ; CATIONES ; Central nervous system ; Crosses, Genetic ; Drosophila ; Drosophila - genetics ; Drosophila - physiology ; DROSOPHILA MELANOGASTER ; Embryos ; Ethyl Methanesulfonate ; Exocytosis ; Female ; Genes, Lethal ; Hatching ; Larvae ; Male ; Membrane Glycoproteins - deficiency ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - physiology ; Mutagenesis ; NERF ; Nerve Tissue Proteins - deficiency ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - physiology ; NERVIOS ; Nervous system ; NEUROFISIOLOGIA ; NEUROPHYSIOLOGIE ; PROTEINAS ; PROTEINE ; Sensors ; SISTEMA NERVIOSO ; Synapses ; Synapses - physiology ; Synaptic transmission ; Synaptic Transmission - physiology ; Synaptic Vesicles - physiology ; Synaptotagmins ; SYSTEME NERVEUX ; TEJIDOS ANIMALES ; TISSU ANIMAL</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1994-10, Vol.91 (22), p.10727-10731</ispartof><rights>Copyright 1994 The National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 25, 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-65b340e853418956fc5115feb66f7bad15323840ce6c7032a2e2f8734bf8dc4c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/91/22.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2366103$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2366103$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7938019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Broadie, K. (University of Cambridge, Cambridge, United Kingdom)</creatorcontrib><creatorcontrib>Bellen, H.J</creatorcontrib><creatorcontrib>DiAntonio, A</creatorcontrib><creatorcontrib>Littleton, J.T</creatorcontrib><creatorcontrib>Schwarz, T.L</creatorcontrib><title>Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence of synaptotagmin, synaptic transmission is dramatically impaired but is not abolished. In null mutants, evoked vesicle release is decreased by a factor of 10. Moreover, the fidelity of excitation-secretion coupling is impaired so that a given stimulus generates a more variable amount of secretion. However, this residual evoked release shows Ca2+-dependence similar to normal release, suggesting either that synaptotagmin is not the Ca2+ sensor or that a second, independent Ca2+ sensor exists. While evoked transmission is suppressed, the rate of spontaneous vesicle fusion is increased by a factor of 5. We conclude that synaptotagmin is not an absolutely essential component of the Ca2+-dependent secretion pathway in synaptic transmission but is necessary for normal levels of transmission. Our data support a model in which synaptotagmin functions as a negative regulator of spontaneous vesicle fusion and acts to increase the efficiency of excitation-secretion coupling during synaptic transmission</description><subject>Animals</subject><subject>Biochemistry</subject><subject>CALCIO</subject><subject>CALCIUM</subject><subject>Calcium - metabolism</subject><subject>Calcium-Binding Proteins</subject><subject>CATION</subject><subject>CATIONES</subject><subject>Central nervous system</subject><subject>Crosses, Genetic</subject><subject>Drosophila</subject><subject>Drosophila - genetics</subject><subject>Drosophila - physiology</subject><subject>DROSOPHILA MELANOGASTER</subject><subject>Embryos</subject><subject>Ethyl Methanesulfonate</subject><subject>Exocytosis</subject><subject>Female</subject><subject>Genes, Lethal</subject><subject>Hatching</subject><subject>Larvae</subject><subject>Male</subject><subject>Membrane Glycoproteins - deficiency</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - physiology</subject><subject>Mutagenesis</subject><subject>NERF</subject><subject>Nerve Tissue Proteins - deficiency</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>NERVIOS</subject><subject>Nervous system</subject><subject>NEUROFISIOLOGIA</subject><subject>NEUROPHYSIOLOGIE</subject><subject>PROTEINAS</subject><subject>PROTEINE</subject><subject>Sensors</subject><subject>SISTEMA NERVIOSO</subject><subject>Synapses</subject><subject>Synapses - physiology</subject><subject>Synaptic transmission</subject><subject>Synaptic Transmission - physiology</subject><subject>Synaptic Vesicles - physiology</subject><subject>Synaptotagmins</subject><subject>SYSTEME NERVEUX</subject><subject>TEJIDOS ANIMALES</subject><subject>TISSU ANIMAL</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><recordid>eNp9UU1rFDEYDqLUdfUuojh48jLbfM8Eeiml1ULBg-1NCJlMsmaZTcYkI-2_N-Osi7309CZ5PvLyPAC8RXCDYENOR6_SRqANxvMdN8_ACkGBak4FfA5WEOKmbimmL8GrlHYQQsFaeAJOGkFaiMQK_DjvkvHaVMFW6cGrMYestnvnq96lOI05VeZeu6yyC75ORkcznyodpnFwflv1U5zHonW6ylH5tHcpFdZr8MKqIZk3h7kGd1eXtxdf65tvX64vzm9qzRDJNWcdodC0jFDUCsZteUbMmo5z23SqR4xg0lKoDdcNJFhhg23bENrZttdUkzU4W3zHqdubXhtfthjkGN1exQcZlJOPEe9-ym34LSkrgRT5p4M8hl-TSVnuwhR92VhiiEjJqfy6BnAh6RhSisYe7RGUcxdy7kIKJDGWf7sokg__r3UUHMIv-McDPiv_oY8dPj_NkHYahmzuc6G-X6i7lEM8cjHhHEFS4HcLbFWQahtdknffBcMNx4T8AQJgsm8</recordid><startdate>19941025</startdate><enddate>19941025</enddate><creator>Broadie, K. 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(University of Cambridge, Cambridge, United Kingdom) ; Bellen, H.J ; DiAntonio, A ; Littleton, J.T ; Schwarz, T.L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-65b340e853418956fc5115feb66f7bad15323840ce6c7032a2e2f8734bf8dc4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>CALCIO</topic><topic>CALCIUM</topic><topic>Calcium - metabolism</topic><topic>Calcium-Binding Proteins</topic><topic>CATION</topic><topic>CATIONES</topic><topic>Central nervous system</topic><topic>Crosses, Genetic</topic><topic>Drosophila</topic><topic>Drosophila - genetics</topic><topic>Drosophila - physiology</topic><topic>DROSOPHILA MELANOGASTER</topic><topic>Embryos</topic><topic>Ethyl Methanesulfonate</topic><topic>Exocytosis</topic><topic>Female</topic><topic>Genes, Lethal</topic><topic>Hatching</topic><topic>Larvae</topic><topic>Male</topic><topic>Membrane Glycoproteins - deficiency</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - physiology</topic><topic>Mutagenesis</topic><topic>NERF</topic><topic>Nerve Tissue Proteins - deficiency</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>NERVIOS</topic><topic>Nervous system</topic><topic>NEUROFISIOLOGIA</topic><topic>NEUROPHYSIOLOGIE</topic><topic>PROTEINAS</topic><topic>PROTEINE</topic><topic>Sensors</topic><topic>SISTEMA NERVIOSO</topic><topic>Synapses</topic><topic>Synapses - physiology</topic><topic>Synaptic transmission</topic><topic>Synaptic Transmission - physiology</topic><topic>Synaptic Vesicles - physiology</topic><topic>Synaptotagmins</topic><topic>SYSTEME NERVEUX</topic><topic>TEJIDOS ANIMALES</topic><topic>TISSU ANIMAL</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Broadie, K. 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(University of Cambridge, Cambridge, United Kingdom)</au><au>Bellen, H.J</au><au>DiAntonio, A</au><au>Littleton, J.T</au><au>Schwarz, T.L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1994-10-25</date><risdate>1994</risdate><volume>91</volume><issue>22</issue><spage>10727</spage><epage>10731</epage><pages>10727-10731</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Synaptotagmin is an integral synaptic vesicle protein proposed to be involved in Ca2+-dependent exocytosis during synaptic transmission. Null mutations in synaptotagmin have been made in Drosophila, and the protein's in vivo function has been assayed at the neuromuscular synapse. in the absence of synaptotagmin, synaptic transmission is dramatically impaired but is not abolished. In null mutants, evoked vesicle release is decreased by a factor of 10. Moreover, the fidelity of excitation-secretion coupling is impaired so that a given stimulus generates a more variable amount of secretion. However, this residual evoked release shows Ca2+-dependence similar to normal release, suggesting either that synaptotagmin is not the Ca2+ sensor or that a second, independent Ca2+ sensor exists. While evoked transmission is suppressed, the rate of spontaneous vesicle fusion is increased by a factor of 5. We conclude that synaptotagmin is not an absolutely essential component of the Ca2+-dependent secretion pathway in synaptic transmission but is necessary for normal levels of transmission. Our data support a model in which synaptotagmin functions as a negative regulator of spontaneous vesicle fusion and acts to increase the efficiency of excitation-secretion coupling during synaptic transmission</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>7938019</pmid><doi>10.1073/pnas.91.22.10727</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biochemistry CALCIO CALCIUM Calcium - metabolism Calcium-Binding Proteins CATION CATIONES Central nervous system Crosses, Genetic Drosophila Drosophila - genetics Drosophila - physiology DROSOPHILA MELANOGASTER Embryos Ethyl Methanesulfonate Exocytosis Female Genes, Lethal Hatching Larvae Male Membrane Glycoproteins - deficiency Membrane Glycoproteins - genetics Membrane Glycoproteins - physiology Mutagenesis NERF Nerve Tissue Proteins - deficiency Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology NERVIOS Nervous system NEUROFISIOLOGIA NEUROPHYSIOLOGIE PROTEINAS PROTEINE Sensors SISTEMA NERVIOSO Synapses Synapses - physiology Synaptic transmission Synaptic Transmission - physiology Synaptic Vesicles - physiology Synaptotagmins SYSTEME NERVEUX TEJIDOS ANIMALES TISSU ANIMAL |
title | Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission |
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