Ca(2+)-synaptotagmin directly regulates t-SNARE function during reconstituted membrane fusion
- PMID: 16565726
- DOI: 10.1038/nsmb1076
Ca(2+)-synaptotagmin directly regulates t-SNARE function during reconstituted membrane fusion
Abstract
In nerve terminals, exocytosis is mediated by SNARE proteins and regulated by Ca(2+) and synaptotagmin-1 (syt). Ca(2+) promotes the interaction of syt with anionic phospholipids and the target membrane SNAREs (t-SNAREs) SNAP-25 and syntaxin. Here, we have used a defined reconstituted fusion assay to determine directly whether syt-t-SNARE interactions couple Ca(2+) to membrane fusion by comparing the effects of Ca(2+)-syt on neuronal (SNAP-25, syntaxin and synaptobrevin) and yeast (Sso1p, Sec9c and Snc2p) SNAREs. Ca(2+)-syt aggregated neuronal and yeast SNARE liposomes to similar extents via interactions with anionic phospholipids. However, Ca(2+)-syt was able to bind and stimulate fusion mediated by only neuronal SNAREs and had no effect on yeast SNAREs. Thus, Ca(2+)-syt regulates fusion through direct interactions with t-SNAREs and not solely through aggregation of vesicles. Ca(2+)-syt drove assembly of SNAP-25 onto membrane-embedded syntaxin, providing direct evidence that Ca(2+)-syt alters t-SNARE structure.
Comment in
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Synaptotagmin: fusogenic role for calcium sensor?Nat Struct Mol Biol. 2006 Apr;13(4):301-3. doi: 10.1038/nsmb0406-301. Nat Struct Mol Biol. 2006. PMID: 16715046 No abstract available.
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