Struktur-Funktions Analyse der aktiven Zone in Drosophila

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Synaptic active zone (AZ) membranes mediate the Ca2+-triggered fusion of synaptic vesicles (SVs) and are associated with macromolecular cytomatrices. CAST/ERCfamily member Bruchpilot (BRP), a coiled-coil rich protein of 200 kD, we previously showed to be essential for cytomatrix (T-bar) formation, Ca2+-channel clustering and patterned synaptic plasticity in Drosophila. Our recent analysis showed that BRP is a direct building block of T-bars, with its N-terminus mediating Ca2+-channel clustering activity for improved vesicle release probability and its very C-terminus end tethering SVs to allow their efficient recruitment during extensive synaptic use. Several BRP isoforms (85, 170, 190 kD) we found, containing either one or both of these shortterm plasticity-relevant domains, which obviously are differentially expressed between synapse-types of Drosophila. We now plan to further describe the isoform spectrum of BRP types and establish specific genetic access to these isoforms. Moreover, these isoforms shall be functionally characterized (synaptic transmission, short-term plasticity, structural role within T-bar assembly) at both, the NMJ model synapse as well as at central synapses of Drosophila of genetically engineered flies. We hope that this project prepares grounds to genetically re-engineer BRP isoforms to allow defined changes of functional performance (particularly short-term plasticity) at defined synapse populations of the Drosophila CNS and PNS.