Abstract

The majority of rapid cell-to-cell communication within the nervous system makes use of chemical synapses. As a basis to understand how synapses process and store information, the molecular organization of presynaptic active zones, the places where neurotransmitter filled synaptic vesicles (SVs) get released, is a focus of intense investigation. We previously identified two conserved scaffold proteins for presynaptic active zone organization, Bruchpilot (BRP) and Rim-binding protein (RimBP)1,2, which are essential for structural organization and efficient neurotransmitter release at active zones in Drosophila. To overcome the resolution limit of standard light microscopy precluding the study of sub-synapse organization, we use super-resolution light microscopy (stimulated emission depletion microscopy, STED ). Thus, functional molecular architectures connecting scaffold proteins with Ca2+ channels and release machinery3 could be effectively studied. An evolutionary conserved design emerges where scaffold protein based SV “release slots” operate as unitary building blocks in the control of SV release regulation.

1. Liu KS, Siebert M, Mertel S, et al. RIM -binding protein, a central part of the active zone, is essential for neurotransmitter release. Science 2011;334:1565-9. 2. Kittel RJ, Wichmann C, Rasse TM, et al. Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 2006;312:1051-4. 3. Bohme MA, Beis C, Reddy-Alla S, et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca(2+) channel-vesicle coupling. Nature neuroscience 2016;19:1311-20.