Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/103874 https://doi.org/10.7554/eLife.64527 |
Resumo: | Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming as a prelude to fast and slow exocytosis triggering. |
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7160 |
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Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent primingSNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle primingAnimalsCalciumCell MembraneChromaffin CellsElectron Microscope TomographyExocytosisIntracellular Signaling Peptides and ProteinsMembrane FusionMiceMice, Inbred C57BLNerve Tissue ProteinsSecretory VesiclesSynaptotagminsSynaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming as a prelude to fast and slow exocytosis triggering.eLife Sciences Publications2021-03-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103874http://hdl.handle.net/10316/103874https://doi.org/10.7554/eLife.64527eng2050-084XTawfik, BassamMartins, Joana SHouy, SébastienImig, CordeliaPinheiro, Paulo S.Wojcik, Sonja MBrose, NilsCooper, Benjamin HSørensen, Jakob Balslevinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-12-06T21:39:35Zoai:estudogeral.uc.pt:10316/103874Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:38.455679Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
title |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
spellingShingle |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming Tawfik, Bassam SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming Animals Calcium Cell Membrane Chromaffin Cells Electron Microscope Tomography Exocytosis Intracellular Signaling Peptides and Proteins Membrane Fusion Mice Mice, Inbred C57BL Nerve Tissue Proteins Secretory Vesicles Synaptotagmins |
title_short |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
title_full |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
title_fullStr |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
title_full_unstemmed |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
title_sort |
Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming |
author |
Tawfik, Bassam |
author_facet |
Tawfik, Bassam Martins, Joana S Houy, Sébastien Imig, Cordelia Pinheiro, Paulo S. Wojcik, Sonja M Brose, Nils Cooper, Benjamin H Sørensen, Jakob Balslev |
author_role |
author |
author2 |
Martins, Joana S Houy, Sébastien Imig, Cordelia Pinheiro, Paulo S. Wojcik, Sonja M Brose, Nils Cooper, Benjamin H Sørensen, Jakob Balslev |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Tawfik, Bassam Martins, Joana S Houy, Sébastien Imig, Cordelia Pinheiro, Paulo S. Wojcik, Sonja M Brose, Nils Cooper, Benjamin H Sørensen, Jakob Balslev |
dc.subject.por.fl_str_mv |
SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming Animals Calcium Cell Membrane Chromaffin Cells Electron Microscope Tomography Exocytosis Intracellular Signaling Peptides and Proteins Membrane Fusion Mice Mice, Inbred C57BL Nerve Tissue Proteins Secretory Vesicles Synaptotagmins |
topic |
SNARE-proteins; capacitance measurements; chromaffin cell; mouse; neuroscience; neurotransmitter release; synaptotagmin-7; vesicle priming Animals Calcium Cell Membrane Chromaffin Cells Electron Microscope Tomography Exocytosis Intracellular Signaling Peptides and Proteins Membrane Fusion Mice Mice, Inbred C57BL Nerve Tissue Proteins Secretory Vesicles Synaptotagmins |
description |
Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming as a prelude to fast and slow exocytosis triggering. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-03-22 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/103874 http://hdl.handle.net/10316/103874 https://doi.org/10.7554/eLife.64527 |
url |
http://hdl.handle.net/10316/103874 https://doi.org/10.7554/eLife.64527 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2050-084X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
eLife Sciences Publications |
publisher.none.fl_str_mv |
eLife Sciences Publications |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134098450546688 |