RIM-binding proteins recruit BK-channels to presynaptic release sites adjacent to voltage-gated Ca 2+ -channels.

The active zone of presynaptic nerve terminals organizes the neurotransmitter release machinery, thereby enabling fast Ca2+ -triggered synaptic vesicle exocytosis. BK-channels are Ca2+ -activated large-conductance K+ -channels that require close proximity to Ca2+ -channels for activation and control Ca2+ -triggered neurotransmitter release by accelerating membrane repolarization during action potential firing. How BK-channels are recruited to presynaptic Ca2+ -channels, however, is unknown. Here, we show that RBPs (for RIM-binding proteins), which are evolutionarily conserved active zone proteins containing SH3- and FN3-domains, directly bind to BK-channels. We find that RBPs interact with RIMs and Ca2+ -channels via their SH3-domains, but to BK-channels via their FN3-domains. Deletion of RBPs in calyx of Held synapses decreased and decelerated presynaptic BK-currents and depleted BK-channels from active zones. Our data suggest that RBPs recruit BK-channels into a RIM-based macromolecular active zone complex that includes Ca2+ -channels, synaptic vesicles, and the membrane fusion machinery, thereby enabling tight spatio-temporal coupling of Ca2+ -influx to Ca2+ -triggered neurotransmitter release in a presynaptic terminal.