RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca2+ channels

Ca2+ 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 Ca2+ channels in hair cells, photoreceptors, and neurons, interact with a,p (L type) and alpha(1B) (N type) Ca2+ channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in a, subunits and Rab3-interacting molecules (RIMs). Overexpression in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs and a, 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 Ca2+ channels and the SNARE complex.