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

J. Biol. Chem., Vol. 282, Issue 39, 28431-28440, September 28, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/39/28431    most recent M706176200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Correll, R. N. Articles by Andres, D. A. Search for Related Content PubMed PubMed Citation Articles by Correll, R. N. Articles by Andres, D. A. Social Bookmarking                      What's this?

Plasma Membrane Targeting Is Essential for Rem-mediated Ca²⁺ Channel Inhibition^*

Robert N. Correll, Chunyan Pang, Brian S. Finlin, Alexandria M. Dailey, Jonathan Satin¹, and Douglas A. Andres²

From the Departments of Molecular and Cellular Biochemistry and Physiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0509

The small GTPase Rem is a potent negative regulator of high voltage-activated Ca²⁺ channels and a known interacting partner for Ca²⁺ channel accessory subunits. The mechanism for Rem-mediated channel inhibition remains controversial, although it has been proposed that Ca_V association is required. Previous work has shown that a C-terminal truncation of Rem (Rem-(1–265)) displays reduced in vivo binding to membrane-localized 2a and lacks channel regulatory function. In this paper, we describe a role for the Rem C terminus in plasma membrane localization through association with phosphatidylinositol lipids. Moreover, Rem-(1–265) can associate with 2a in vitro and 1b in vivo, suggesting that the C terminus does not directly participate in Ca_V association. Despite demonstrated 1b binding, Rem-(1–265) was not capable of regulating a Ca_V1.2-1b channel complex, indicating that subunit binding is not sufficient for channel regulation. However, fusion of the CAAX domain from K-Ras4B or H-Ras to the Rem-(1–265) C terminus restored membrane localization and Ca²⁺ channel regulation, suggesting that binding and membrane localization are independent events required for channel inhibition.

Received for publication, July 26, 2007

^* This work was supported by Public Health Service Grants HL072936 (to D. A. A.), HL074091 (to J. S.), and P20 RR20171 from the National Center for Research Resources, National Institutes of Health (NIH) (to D. A. A.), an American Diabetes Association Junior Faculty award (to B. S. F.), and an American Heart Association predoctoral fellowship and NIH Interdisciplinary Cardiovascular Training Grant T32 HL072743 (to R. N. C.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ An Established Investigator of the American Heart Association.

² To whom correspondence should be addressed: Dept. of Molecular and Cellular Biochemistry, BBSRB Rm. B-179, University of Kentucky College of Medicine, 741 S. Limestone St., Lexington, KY 40536-0509. Tel.: 859-257-6775; Fax: 859-323-1037; E-mail: dandres{at}uky.edu.

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