Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1.
Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.
Lee
Amy
A
Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195-7280, USA.
Westenbroek
Ruth E
RE
Haeseleer
Françoise
F
Palczewski
Krzysztof
K
Scheuer
Todd
T
Catterall
William A
WA
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D015800:Protozoan Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020798:Two-Hybrid System Techniques
D002118:Calcium; D020864:Calcium Channels, N-Type; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002614:Chelating Agents; D004533:Egtazic Acid; D021122:Protein Subunits; D015800:Protozoan Proteins; C093239:calcium-binding protein 1, Dictyostelium discoideum