Differential interactions of the C terminus and the cytoplasmic I-II loop of neuronal Ca2+ channels with G-protein alpha and beta gamma subunits. I. Molecular determination.

The Journal of Biological Chemistry
T FurukawaM Yoshii

Abstract

Interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels were investigated using the Xenopus oocyte expression system. Gi3alpha was found to inhibit both N- and P/Q-type channels by receptor agonists, whereas Gbeta1 gamma2 was responsible for prepulse facilitation of N-type channels. L-type channels (alpha1C) were not regulated by Galpha or Gbeta gamma. For N-type, prepulse facilitation mediated via Gbeta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted or replaced with the alpha1C loop 1. Galpha-mediated inhibitions were also impaired by substitution of the alpha1C loop 1, but only when the C terminus was deleted. For P/Q-type, by contrast, deletion of the C terminus alone diminished Galpha-mediated inhibition. Moreover, a chimera of L-type with the alpha1B loop 1 gained Gbeta gamma-dependent facilitation, whereas an L-type chimera with the N- or P/Q-type C terminus gained Galpha-mediated inhibition. These findings provide evidence that loop 1 of N-type channels is a regulatory site for Gbeta gamma and the C termini of P/Q- and N-types for Galpha.

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Citations

Mar 31, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Holly B Kordasiewicz, Christopher M Gomez
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Jun 13, 2000·Alzheimer Disease and Associated Disorders·M YoshiiT Shiotani
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Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·H ZhongW A Catterall
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Nov 16, 2004·Annals of the New York Academy of Sciences·Mitsunobu YoshiiToshihide Nukada
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Jan 1, 2015·Molecular Pharmacology·Juliane Proft, Norbert Weiss
Sep 27, 2008·Neuron·William A Catterall, Alexandra P Few

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