Biochemistry

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Science  08 Aug 2008:
Vol. 321, Issue 5890, pp. 746-747
DOI: 10.1126/science.321.5890.746c

Synaptotagmin 1 (Syt1) is a Ca2+-binding protein in synaptic vesicles and triggers rapid exocytosis (vesicle fusion with the plasma membrane) in response to Ca2+ influx. Fusion mediated by Syt1 and SNAREs (a family of membrane fusion proteins) can be studied in vitro by mixing two populations of vesicles that have been reconstituted with SNAREs: one population with target membrane-associated SNAREs and one with the synaptic vesicle SNARE synaptobrevin 2. Addition of the soluble cytoplasmic domain of Syt1 in the presence of Ca2+ triggers fusion, whereas addition of the soluble cytoplasmic domain of synaptobrevin (cd-syb) immediately blocks fusion through competitive inhibition. Chicka et al. use this assay to show that both the rate and extent of Ca2+-triggered fusion are increased when the vesicle mixture is pre-incubated with Syt1 for 20 min before addition of Ca2+. Furthermore, fusion is no longer immediately inhibited by cd-syb when vesicles have been pre-incubated with Syt1, demonstrating the presence of a population of docked vesicles in which SNAREs from opposing membranes are already paired. Syt1, therefore, acts in the absence of Ca2+ to increase the number of docked fusion-ready vesicles, possibly by stalling partially assembled SNARE complexes. In vivo, this function of Syt1 may contribute to the buildup of docked vesicles, which is essential for the rapid and coordinated release of neurotransmitter. — NM*

Nat. Struct. Mol. Biol. 10.1038/nsmb.1463 (2008).

  • * Nilah Monnier is a summer intern in Science's editorial department.

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