title: Differential roles for snapin and synaptotagmin in the synaptic vesicle cycle.
abstract: Evoked synaptic transmission is dependent on interactions between the calcium sensor Synaptotagmin I and the SNARE complex, comprised of Syntaxin, SNAP-25, and Synaptobrevin. Recent evidence suggests that Snapin may be an important intermediate in this process, through simultaneous interactions of Snapin dimers with SNAP-25 and Synaptotagmin. In support of this model, cultured neurons derived from embryonically lethal Snapin null mutant mice exhibit desynchronized release and a reduced readily releasable vesicle pool. Based on evidence that a dimerization-defective Snapin mutation specifically disrupts priming, Snapin is hypothesized to stabilize primed vesicles by structurally coupling Synaptotagmin and SNAP-25. To explore this model in vivo we examined synaptic transmission in viable, adult C. elegans Snapin (snpn-1) mutants. The kinetics of synaptic transmission were unaffected at snpn-1 mutant neuromuscular junctions (NMJs), but the number of docked, fusion competent vesicles was significantly reduced. However, analyses of snt-1 and snt-1;snpn-1 double mutants suggest that the docking role of SNPN-1 is independent of Synaptotagmin. Based on these results we propose that the primary role of Snapin in C. elegans is to promote vesicle priming, consistent with the stabilization of SNARE complex formation through established interactions with SNAP-25 upstream of the actions of Synaptotagmin in calcium-sensing and endocytosis.
authors.affiliation: Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Szi-Chieh
authors.initials: SC
authors.lastname: Yu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Klosterman
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Martin
authors.forename: Elena O
authors.initials: EO
authors.lastname: Gracheva
authors.forename: Janet E
authors.initials: JE
authors.lastname: Richmond
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D013572:Synaptic Vesicles / Q000378:metabolism*; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D033921:Vesicular Transport Proteins; C583094:snpn-1 protein, C elegans; D050857:Synaptotagmins