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J. Biol. Chem., Vol. 282, Issue 43, 31631-31642, October 26, 2007

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Tetraspanin CD151 Promotes Cell Migration by Regulating Integrin Trafficking^*

Li Liu, Bo He, Wei M. Liu, Dongming Zhou, John V. Cox, and Xin A. Zhang¹

From the Vascular Biology Center, Cancer Institute, Department of Medicine and Department of Molecular Science, University of Tennessee Health Science Center, Memphis, Tennessee 38163

Regulation of cell migration is an important feature of tetraspanin CD151. Although it is well established that CD151 physically associates with integrins, the mechanism by which CD151 regulates integrin-dependent cell migration is basically unknown. Given the fact that CD151 is localized in both the plasma membrane and intracellular vesicles, we found that CD151 and its associated 31, 51, and 61 integrins undergo endocytosis and accumulate in the same intracellular vesicular compartments. CD151 contains a YRSL sequence, a YXX type of endocytosis/sorting motif, in its C-terminal cytoplasmic domain. Mutation of this motif markedly attenuated CD151 internalization. The loss of CD151 trafficking completely abrogated CD151-promoted cell migration on extracellular matrices such as laminin and diminished the internalization of its associated integrins, indicating a critical role for integrin trafficking in regulating cell motility. In conclusion, the YXX motif-mediated internalization of CD151 promotes integrin-dependent cell migration by modulating the endocytosis and/or vesicular trafficking of its associated integrins.

Received for publication, February 7, 2007 , and in revised form, August 20, 2007.

^* This work was supported by American Heart Association Grants 0160238B and 0335299N and National Institutes of Health Grant CA96991 (to X. A. 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.

¹ To whom correspondence should be addressed: Vascular Biology, Coleman H300, 956 Ct. Ave., Memphis, TN 38163. Tel.: 901-448-3448; Fax: 901-448-7181; E-mail: xazhang{at}utmem.edu.

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