{"corpus_id":205434152,"paper_sha":"f5ef0cd2f6f6f2e74c13f322891624efb9588713","doi":"10.1038/nn.3013","arxiv_id":null,"pmid":22197832,"pmcid":"3435110","mag_id":2026784698,"dblp_id":null,"acl_id":null,"title":"Uncoupling the roles of synaptotagmin I as a dual Ca2+ sensor during endo- and exocytosis of synaptic vesicles","year":2011,"publication_date":"2011-12-20","venue":"Nature Neuroscience","journal":{"name":"Nature neuroscience","pages":"243 - 249","volume":"15"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":50,"citation_count":70,"influential_citation_count":5,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Action Potentials","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D000200"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Animals, Newborn","mj":false,"ui":"D000831"},{"d":"Biophysics","mj":false,"ui":"D001703"},{"d":"Calcium","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002118"},{"d":"Cells, Cultured","mj":false,"ui":"D002478"},{"d":"Chromaffin Cells","mj":false,"ui":"D019439"},{"d":"Egtazic Acid","mj":false,"qs":[{"q":"analogs & derivatives","mj":false,"ui":"Q000031"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D004533"},{"d":"Electric Stimulation","mj":false,"ui":"D004558"},{"d":"Endocytosis","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D004705"},{"d":"Excitatory Postsynaptic Potentials","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D019706"},{"d":"Exocytosis","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D005089"},{"d":"GAP-43 Protein","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D019922"},{"d":"Green Fluorescent Proteins","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D049452"},{"d":"Hippocampus","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"}],"ui":"D006624"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Models, Biological","mj":false,"ui":"D008954"},{"d":"Mutagenesis","mj":false,"qs":[{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D016296"},{"d":"Neurons","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"physiology","mj":false,"ui":"Q000502"}],"ui":"D009474"},{"d":"Patch-Clamp Techniques","mj":false,"ui":"D018408"},{"d":"Protein Structure, Tertiary","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D017434"},{"d":"Synapses","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D013569"},{"d":"Synaptic Vesicles","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D013572"},{"d":"Synaptotagmin I","mj":false,"qs":[{"q":"deficiency","mj":false,"ui":"Q000172"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D050863"},{"d":"Transfection","mj":false,"ui":"D014162"}],"chemicals":[{"n":"GAP-43 Protein","ui":"D019922","reg":"0"},{"n":"Synaptotagmin I","ui":"D050863","reg":"0"},{"n":"1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester","ui":"C070379","reg":"139890-68-9"},{"n":"Green Fluorescent Proteins","ui":"D049452","reg":"147336-22-9"},{"n":"Egtazic Acid","ui":"D004533","reg":"526U7A2651"},{"n":"Calcium","ui":"D002118","reg":"SY7Q814VUP"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Synaptotagmin I (syt1) is required for normal rates of synaptic vesicle endo- and exocytosis. However, whether the kinetic defects observed during endocytosis in Syt1 knockout neurons are secondary to defective exocytosis or whether syt1 directly regulates the rate of vesicle retrieval remains unknown. To address this question, we sought to dissociate these two activities. We uncoupled the function of syt1 in exo- and endocytosis in mouse neurons either by re-targeting the protein or via mutagenesis of its tandem C2 domains. The effect of these manipulations on exo- and endocytosis were analyzed using electrophysiology, in conjunction with optical imaging of the vesicle cycle. Our results indicate that syt1 is directly involved in endocytosis. Notably, either of the C2 domains of syt1, C2A or C2B, was able to function as a Ca2+ sensor for endocytosis. 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