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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark
TETHERING VESICLES TO THE ACTIVE ZONE CYTOMATRIX PROMOTES SUSTAINED SYNAPTIC RELEASE
Abstract number: O-SUN-8-3
HALLERMANN1 S, KITTEL1 RJ, WICHMANN1 C, WEYHERSMULLER1 A, FOUQUET1 W, MERTEL1 S, OWALD1 D, EIMER1 S, DEPPNER1 H, SCHWARZEL1 M, SIGRIST1 SJ, HECKMANN1 M
Objective: At presynaptic active zones (AZs), the frequently observed tethering of synaptic vesicles to an electron-dense cytomatrix represents a process of largely unknown functional significance. Methods: Here, we studied both the structure (electron and stimulated emission depletion microscopy) and the function (electrophysiology) of the AZ cytomatrix and investigated the relation between vesicle tethering and recruitment at the Drosophila neuromuscular junction of different genotypes. Results: A large-scale chemical mutagenesis screen identified an allele of the Drosophila AZ protein Bruchpilot (BRP), missing only the last 1% of the C-terminal amino acids (17 of 1740). In these mutants, the Ca2+ channel clustering and synchronous release were unaffected and in electron microscopy, the AZ cytomatrix appeared normal. However, tethering of synaptic vesicles to the AZ cytomatrix and vesicle recruitment were severely impaired. Consistently, sustained release was also impaired in BRP mutants lacking ~30 and ~50 % of the C terminal amino acids. Conclusion: These results causally link, with intra-molecular precision, the tethering of vesicles to the AZ cytomatrix to their efficient release during sustained activity.
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Acta Physiologica 2010; Volume 198, Supplement 677 :O-SUN-8-3