RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels.
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 alpha(1D) (L type) and alpha(1B) (N type) Ca(2+) channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in alpha(1) subunits and Rab3-interacting molecules (RIMs). Overexpression in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs and alpha(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.
Hibino
H
H
Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Pironkova
R
R
Onwumere
O
O
Vologodskaia
M
M
Hudspeth
A J
AJ
Lesage
F
F
D000818:Animals; D001921:Brain / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002645:Chickens; D005089:Exocytosis / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors; D006198:Hair Cells, Auditory / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D021122:Protein Subunits; C092115:Rab3ip protein, rat; D011993:Recombinant Fusion Proteins