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J. Biol. Chem., Vol. 280, Issue 27, 25840-25848, July 8, 2005

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A Cryptic Rab1-binding Site in the p115 Tethering Protein^*

Matthew Beard, Ayano Satoh¶, James Shorter||, and Graham Warren**

From the Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, the Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut 06520, and the ^||Lindquist Lab, Whitehead Institute, Cambridge, Massachusetts 02142

Small GTPases and coiled-coil proteins of the golgin family help to tether COPI vesicles to Golgi membranes. At the cis-side of the Golgi, the Rab1 GTPase binds directly to each of three coiled-coil proteins: p115, GM130, and as now shown, Giantin. Rab1 binds to a coiled-coil region within the tail domain of p115 and this binding is inhibited by the C-terminal, acidic domain of p115. Furthermore, GM130 and Giantin bind to the acidic domain of p115 and stimulate p115 binding to Rab1, suggesting that p115 binding to Rab1 is regulated. Regulation of this interaction by proteins such as GM130 and Giantin may control the membrane recruitment of p115 by Rab1.

Received for publication, April 11, 2005 , and in revised form, May 5, 2005.

^* This work was supported in part by National Institutes of Health and the Ludwig Institute for Cancer Research. 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 and S2 and Table S1.

This article was selected as a Paper of the Week.

^¶ Supported by the American Heart Association.

^** To whom correspondence should be addressed: Dept. of Cell Biology, Ludwig Inst. for Cancer Research, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520-8002. Tel.: 203-785-5058; Fax: 203-785-4301; E-mail: graham.warren{at}yale.edu.

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