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

J. Biol. Chem., Vol. 283, Issue 45, 30868-30878, November 7, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/45/30868    most recent M804054200v1 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 Baugher, P. J. Articles by Richmond, A. Search for Related Content PubMed PubMed Citation Articles by Baugher, P. J. Articles by Richmond, A. Social Bookmarking                      What's this?

The Carboxyl-terminal PDZ Ligand Motif of Chemokine Receptor CXCR2 Modulates Post-endocytic Sorting and Cellular Chemotaxis^*

Paige J. Baugher and Ann Richmond¹

From the Department of Veterans Affairs, Veterans Affairs Medical Center, Nashville, Tennessee 37212-2637 and the Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Adaptor protein interaction with specific peptide motifs found within the intracellular, carboxyl terminus of chemokine receptor CXCR2 has been shown to modulate intracellular trafficking and receptor function. Efficient ligand-induced internalization of this receptor is dependent on the binding of adaptor protein 2 to the specific LLKIL motif found within the carboxyl terminus (1). In this study we show that the carboxyl-terminal type 1 PDZ ligand motif (-STTL) of CXCR2 plays an essential role in both proper intracellular receptor trafficking and efficient cellular chemotaxis. First, we show that CXCR2 is sorted to and degraded in the lysosome upon long-term ligand stimulation. We also show that receptor degradation is not dependent upon receptor ubiquitination, but is instead modulated by the carboxyl-terminal type I PDZ ligand of CXCR2. Deletion of this ligand results in increased degradation, earlier co-localization with the lysosome, and enhanced sorting to the Rab7-positive late endosome. We also show that deletion of this ligand effects neither receptor internalization nor receptor recycling. Furthermore, we demonstrate that deletion of the PDZ ligand motif results in impaired chemotactic response. The data presented here demonstrate that the type I PDZ ligand of CXCR2 acts to both delay lysosomal sorting and facilitate proper chemotactic response.

Received for publication, May 28, 2008 , and in revised form, August 1, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health NCI Grant CA34590 (to A. R.). This work was also supported by Multidisciplinary Basic Research Training in Cancer Grant T32CA09592 (to P. B.), Vanderbilt-Ingram Cancer Center Support Grant CA68485, and a Senior Career Scientist Award from the Department of Veterans Affairs (to A. R.). 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: 771 PRB, 23rd Ave. S. at Pierce, Nashville, TN 37232. Fax: 615-936-2911; E-mail: ann.richmond{at}vanderbilt.edu.

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