RIM Binding Proteins (RBPs) Couple Rab3-Interacting Molecules (RIMs) to Voltage-Gated Ca 2+ Channels

Abstract

Ca 2+ influx through voltage-gated channels initiates the exocytotic fusion of synaptic vesicles to the plasma membrane. Here we show that RIM binding proteins (RBPs), which associate with Ca 2+ channels in hair cells, photoreceptors, and neurons, interact with α 1D (L type) and α 1B (N type) Ca 2+ channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in α 1 subunits and Rab3-interacting molecules (RIMs). Overexpression in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs and α 1 augments the exocytosis triggered by depolarization. RBPs may regulate the strength of synaptic transmission by creating a functional link between the synaptic-vesicle tethering apparatus, which includes RIMs and Rab3, and the fusion machinery, which includes Ca 2+ channels and the SNARE complex.