RGS12 interacts with the SNARE-binding region of the Cav2.2 calcium channel

Ryan W. Richman, Jesse Strock, Melinda D. Hains, Nory Jun Cabanilla, King Kei Lau, David P. Siderovski, María Diversé-Pierluissi

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28 Scopus citations

Abstract

Activation of GABAB receptors in chick dorsal root ganglion (DRG) neurons inhibits the Cav2.2 calcium channel in both a voltage-dependent and voltage-independent manner. The voltage-independent inhibition requires activation of a tyrosine kinase that phosphorylates the α1 subunit of the channel and thereby recruits RGS12, a member of the "regulator of G protein signaling" (RGS) proteins. Here we report that RGS12 binds to the SNARE-binding or "synprint" region (amino acids 726-985) in loop II-III of the calcium channel α1 subunit. A recombinant protein encompassing the N-terminal PTB domain of RGS12 binds to the synprint region in protein overlay and surface plasmon resonance binding assays; this interaction is dependent on tyrosine phosphorylation and yet is within a sequence that differs from the canonical NPXY motif targeted by other PTB domains. In electrophysiological experiments, microinjection of DRG neurons with synprint-derived peptides containing the tyrosine residue Tyr-804 altered the rate of desensitization of neurotransmitter-mediated inhibition of the Cav2.2 calcium channel, whereas peptides centered about a second tyrosine residue, Tyr-815, were without effect. RGS12 from a DRG neuron lysate was precipitated using synprint peptides containing phosphorylated Tyr-804. The high degree of conservation of Tyr-804 in the SNARE-binding region of Ca v2.1 and Cav2.2 calcium channels suggests that this region, in addition to the binding of SNARE proteins, is also important for determining the time course of the modulation of calcium current via tyrosine phosphorylation.

Original languageEnglish
Pages (from-to)1521-1528
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number2
DOIs
StatePublished - 14 Jan 2005

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    Richman, R. W., Strock, J., Hains, M. D., Cabanilla, N. J., Lau, K. K., Siderovski, D. P., & Diversé-Pierluissi, M. (2005). RGS12 interacts with the SNARE-binding region of the Cav2.2 calcium channel. Journal of Biological Chemistry, 280(2), 1521-1528. https://doi.org/10.1074/jbc.M406607200