Bassoon Specifically Controls Presynaptic P/Q-type Ca2+ Channels via RIM-Binding Protein

Voltage-dependent Ca2+ channels (CaVs) represent the principal source of Ca2+ ions that trigger evoked neurotransmitter release from presynaptic boutons. Ca2+ influx is mediated mainly via Ca(V)2.1 (P/Q-type) and Ca(V)2.2 (N-type) channels, which differ in their properties. Their relative contribution to synaptic transmission changes during development and tunes neurotransmission during synaptic plasticity. The mechanism of differential recruitment of Ca(V)2.1 and Ca(V)2.2 to release sites is largely unknown. Here, we show that the presynaptic scaffolding protein Bassoon localizes specifically Ca(V)2.1 to active zones via molecular interaction with the RIM-binding proteins (RBPs). A genetic deletion of Bassoon or an acute interference with Bassoon-RBP interaction reduces synaptic abundance of Ca(V)2.1, weakens P/Q-type Ca2+ current-driven synaptic transmission, and results in higher relative contribution of neurotransmission dependent on Ca(V)2.2. These data establish Bassoon as a major regulator of the molecular composition of the presynaptic neurotransmitter release sites.