HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 28, 29709-29717, July 9, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/28/29709    most recent M308693200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doering, C. J. Articles by Zamponi, G. W. Search for Related Content PubMed PubMed Citation Articles by Doering, C. J. Articles by Zamponi, G. W. Social Bookmarking                      What's this?

A Single G Subunit Locus Controls Cross-talk between Protein Kinase C and G Protein Regulation of N-type Calcium Channels^*

Clinton J. Doering, Alexandra E. Kisilevsky, Zhong-Ping Feng¶, Michelle I. Arnot||, Jean Peloquin, Jawed Hamid, Wendy Barr, Aparna Nirdosh, Brett Simms, Robert J. Winkfein, and Gerald W. Zamponi**

From the Department of Physiology and Biophysics, Cellular and Molecular Neurobiology Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada

The modulation of N-type calcium channels is a key factor in the control of neurotransmitter release. Whereas N-type channels are inhibited by G subunits in a G protein -isoform-dependent manner, channel activity is typically stimulated by activation of protein kinase C (PKC). In addition, there is cross-talk among these pathways, such that PKC-dependent phosphorylation of the G target site on the N-type channel antagonizes subsequent G protein inhibition, albeit only for G₁-mediated responses. The molecular mechanisms that control this G protein subunit subtype-specific regulation have not been described. Here, we show that G protein inhibition of N-type calcium channels is critically dependent on two separate but adjacent 20-amino acid regions of the G subunit, plus a highly conserved Asn-Tyr-Val motif. These regions are distinct from those implicated previously in G signaling to other effectors such as G protein-coupled inward rectifier potassium channels, phospholipase ₂, and adenylyl cyclase, thus raising the possibility that the specificity for G protein signaling to calcium channels might rely on unique G protein structural determinants. In addition, we identify a highly specific locus on the G₁ subunit that serves as a molecular detector of PKC-dependent phosphorylation of the G protein target site on the N-type channel ₁ subunit, thus providing for a molecular basis for G protein-PKC cross-talk. Overall, our results significantly advance our understanding of the molecular details underlying the integration of G protein and PKC signaling pathways at the level of the N-type calcium channel ₁ subunit.

Received for publication, August 6, 2003 , and in revised form, April 9, 2004.

^* This work was supported by an operating grant from the Canadian Institutes of Health Research (to G. W. Z.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

These authors contributed equally to this work.

Recipient of a studentship award from the Alberta Heritage Foundation for Medical Research.

^¶ Supported by postdoctoral fellowships from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada.

^|| Supported by a postdoctoral fellowship from the Heart and Stroke Foundation of Canada.

^** Canadian Institutes of Health Research Investigator. Recipient of a senior scholar award from the Alberta Heritage Foundation for Medical Research. To whom correspondence should be addressed: Dept. of Physiology and Biophysics, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada. Tel.: 403-220-8687; Fax: 403-210-8106; E-mail. Zamponi{at}ucalgary.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. J. Dupre, M. Robitaille, M. Richer, N. Ethier, A. M. Mamarbachi, and T. E. Hebert Dopamine Receptor-interacting Protein 78 Acts as a Molecular Chaperone for G{gamma} Subunits before Assembly with Gbeta J. Biol. Chem., May 4, 2007; 282(18): 13703 - 13715. [Abstract] [Full Text] [PDF]

				H. W. Tedford and G. W. Zamponi Direct G Protein Modulation of Cav2 Calcium Channels Pharmacol. Rev., December 1, 2006; 58(4): 837 - 862. [Abstract] [Full Text] [PDF]

				S. D. DePuy, J. Yao, C. Hu, W. McIntire, I. Bidaud, P. Lory, F. Rastinejad, C. Gonzalez, J. C. Garrison, and P. Q. Barrett The molecular basis for T-type Ca2+ channel inhibition by G protein beta2{gamma}2 subunits PNAS, September 26, 2006; 103(39): 14590 - 14595. [Abstract] [Full Text] [PDF]

				H. W. Tedford, A. E. Kisilevsky, J. B. Peloquin, and G. W. Zamponi Scanning Mutagenesis Reveals a Role for Serine 189 of the Heterotrimeric G-Protein Beta 1 Subunit in the Inhibition of N-Type Calcium Channels J Neurophysiol, July 1, 2006; 96(1): 465 - 470. [Abstract] [Full Text] [PDF]

				R. V. Rebois, M. Robitaille, C. Gales, D. J. Dupre, A. Baragli, P. Trieu, N. Ethier, M. Bouvier, and T. E. Hebert Heterotrimeric G proteins form stable complexes with adenylyl cyclase and Kir3.1 channels in living cells J. Cell Sci., July 1, 2006; 119(13): 2807 - 2818. [Abstract] [Full Text] [PDF]

				X. Li, A. Hummer, J. Han, M. Xie, K. Melnik-Martinez, R. L. Moreno, M. Buck, M. D. Mark, and S. Herlitze G Protein {beta}2 Subunit-derived Peptides for Inhibition and Induction of G Protein Pathways: EXAMINATION OF VOLTAGE-GATED Ca2+ AND G PROTEIN INWARDLY RECTIFYING K+ CHANNELS J. Biol. Chem., June 24, 2005; 280(25): 23945 - 23959. [Abstract] [Full Text] [PDF]