Fusion pore dynamics are regulated by synaptotagmin•t-SNARE interactions
Journal
Neuron
Journal Volume
41
Journal Issue
6
Date Issued
2004-03-25
Author(s)
Abstract
Exocytosis involves the formation of a fusion pore that connects the lumen of secretory vesicles with the extracellular space. Exocytosis from neurons and neuroendocrine cells is tightly regulated by intracellular [Ca 2+ ] and occurs rapidly, but the molecular events that mediate the opening and subsequent dilation of fusion pores remain to be determined. A putative Ca 2+ sensor for release, synaptotagmin I (syt), binds directly to syntaxin and SNAP-25, which are components of a conserved membrane fusion complex. Here, we show that Ca 2+ -triggered syt•SNAP-25 interactions occur rapidly. The tandem C2 domains of syt cooperate to mediate binding to syntaxin/SNAP-25; lengthening the linker that connects C2A and C2B selectively disrupts this interaction. Expression of the linker mutants in PC12 cells results in graded reductions in the stability of fusion pores. Thus, the final step of Ca 2+ -triggered exocytosis is regulated, at least in part, by direct contacts between syt and SNAP-25/syntaxin.
Other Subjects
SNARE protein; synaptosomal associated protein 25; synaptotagmin; article; binding affinity; binding site; calcium cell level; exocytosis; immunohistochemistry; priority journal; protein binding; protein domain; protein expression; protein protein interaction; Animals; Calcium; Calcium Signaling; Calcium-Binding Proteins; Exocytosis; Kinetics; Macromolecular Substances; Membrane Fusion; Membrane Glycoproteins; Membrane Proteins; Mutation; Nerve Tissue Proteins; PC12 Cells; Presynaptic Terminals; Protein Binding; Protein Structure, Tertiary; Qa-SNARE Proteins; Rats; SNARE Proteins; Synaptic Membranes; Synaptic Transmission; Synaptosomal-Associated Protein 25; Synaptotagmin I; Synaptotagmins; Vesicular Transport Proteins
Type
journal article
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