GENERIC 17914059

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0015283, umls-concept:C0084697, umls-concept:C0086597, umls-concept:C0183362, umls-concept:C0205224, umls-concept:C0300824, umls-concept:C0596235, umls-concept:C0851827, umls-concept:C1444748, umls-concept:C1701901, umls-concept:C1704675
pubmed:issue	12
pubmed:dateCreated	2007-11-28
pubmed:abstractText	Synaptotagmins contain tandem C2 domains and function as Ca(2+) sensors for vesicle exocytosis but the mechanism for coupling Ca(2+) rises to membrane fusion remains undefined. Synaptotagmins bind SNAREs, essential components of the membrane fusion machinery, but the role of these interactions in Ca(2+)-triggered vesicle exocytosis has not been directly assessed. We identified sites on synaptotagmin-1 that mediate Ca(2+)-dependent SNAP25 binding by zero-length cross-linking. Mutation of these sites in C2A and C2B eliminated Ca(2+)-dependent synaptotagmin-1 binding to SNAREs without affecting Ca(2+)-dependent membrane binding. The mutants failed to confer Ca(2+) regulation on SNARE-dependent liposome fusion and failed to restore Ca(2+)-triggered vesicle exocytosis in synaptotagmin-deficient PC12 cells. The results provide direct evidence that Ca(2+)-dependent SNARE binding by synaptotagmin is essential for Ca(2+)-triggered vesicle exocytosis and that Ca(2+)-dependent membrane binding by itself is insufficient to trigger fusion. A structure-based model of the SNARE-binding surface of C2A provided a new view of how Ca(2+)-dependent SNARE and membrane binding occur simultaneously.
pubmed:grant	http://linkedlifedata.com/resource/pubmed/grant/5T15LM007359-03, http://linkedlifedata.com/resource/pubmed/grant/DK25861
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pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/9201390
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents, http://linkedlifedata.com/resource/pubmed/chemical/Liposomes, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylserines, http://linkedlifedata.com/resource/pubmed/chemical/SNARE Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Synaptosomal-Associated Protein 25, http://linkedlifedata.com/resource/pubmed/chemical/Synaptotagmins
pubmed:status	MEDLINE
pubmed:month	Dec
pubmed:issn	1059-1524
pubmed:author	pubmed-author:MitchellJ CJC, pubmed-author:LynchK LKL, pubmed-author:LarsenE CEC, pubmed-author:MartinT F JTF

Statements in which the resource exists as a subject.

Predicate

Object

rdf:type

pubmed:Citation

lifeskim:mentions

umls-concept:C0015283, umls-concept:C0084697, umls-concept:C0086597, umls-concept:C0183362, umls-concept:C0205224, umls-concept:C0300824, umls-concept:C0596235, umls-concept:C0851827, umls-concept:C1444748, umls-concept:C1701901, umls-concept:C1704675

pubmed:issue

pubmed:dateCreated

2007-11-28

pubmed:abstractText

Synaptotagmins contain tandem C2 domains and function as Ca(2+) sensors for vesicle exocytosis but the mechanism for coupling Ca(2+) rises to membrane fusion remains undefined. Synaptotagmins bind SNAREs, essential components of the membrane fusion machinery, but the role of these interactions in Ca(2+)-triggered vesicle exocytosis has not been directly assessed. We identified sites on synaptotagmin-1 that mediate Ca(2+)-dependent SNAP25 binding by zero-length cross-linking. Mutation of these sites in C2A and C2B eliminated Ca(2+)-dependent synaptotagmin-1 binding to SNAREs without affecting Ca(2+)-dependent membrane binding. The mutants failed to confer Ca(2+) regulation on SNARE-dependent liposome fusion and failed to restore Ca(2+)-triggered vesicle exocytosis in synaptotagmin-deficient PC12 cells. The results provide direct evidence that Ca(2+)-dependent SNARE binding by synaptotagmin is essential for Ca(2+)-triggered vesicle exocytosis and that Ca(2+)-dependent membrane binding by itself is insufficient to trigger fusion. A structure-based model of the SNARE-binding surface of C2A provided a new view of how Ca(2+)-dependent SNARE and membrane binding occur simultaneously.

pubmed:grant

http://linkedlifedata.com/resource/pubmed/grant/5T15LM007359-03, http://linkedlifedata.com/resource/pubmed/grant/DK25861

pubmed:commentsCorrections

pubmed:language

eng

pubmed:journal

http://linkedlifedata.com/resource/pubmed/journal/9201390

pubmed:citationSubset

pubmed:chemical

pubmed:status

MEDLINE

pubmed:month

Dec

pubmed:issn

1059-1524

pubmed:author

pubmed-author:MitchellJ CJC, pubmed-author:LynchK LKL, pubmed-author:LarsenE CEC, pubmed-author:MartinT F JTF