Prof. Dr. Stephan Sigrist

Institute for Biology and Genetics, Freie Universität Berlin & NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Berlin

Title: An active zone state switch concentrates and immobilizes voltage-gated Ca2+ channels to boost vesicle release

Abstract: At presynaptic active zones (AZs), a conserved scaffold protein architecture controls synaptic vesicle (SV) release by steering the nanoscale distribution and density of voltage-gated Ca2+ channels. Whether and if how presynaptic plasticity mechanisms utilize nanoscale changes of voltage-gated Ca2+ channels remains to be explored. We recently established intravital single-molecule imaging of endogenously tagged Cav2 type-Ca2+ channel Cacophony (Cac) at Drosophila AZs triggered towards homeostatic potentiation. At potentiating AZs, Cac channel numbers increased, their mobility decreased, and their overall distribution became more compact. This compaction seems driven by an interaction connecting the intracellular Ca2+ channel C-term with AZ plasma membrane-close N-term of the ELKS-family scaffold protein Bruchpilot (BRP). As single molecule imaging of BRP pictured an extensive plasticity-driven compaction, our data suggest that switching to a compacted AZ BRP scaffold state concentrates and immobilizes individual Ca 2+ channels to sustain enduring potentiation of AZ release. I will present work to corroborate these statements, and report about our attempts to deeper understand the structural and functional dynamics of AZ scaffolds in development and plasticity.

Please join us prior to the talk for coffee and cookies.