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J. Biol. Chem. 278 (15): 12888-12893

© 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

Heparan Sulfate Regulates Targeting of Syndecan-1 to a Functional Domain on the Cell Surface*

Yang YangDagger , Magne BørsetDagger , J. Kevin LangfordDagger , and Ralph D. SandersonDagger §

From the Departments of Dagger  Pathology and § Anatomy and Neurobiology, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205

In polarized B lymphoid cells, syndecan-1 is targeted specifically to a discrete membrane domain termed the uropod that is located at the cell's trailing edge. Within this functional domain, syndecan-1 promotes cell-cell adhesion and concentration of heparin binding growth factors. The present study reveals the surprising finding that targeting of syndecan-1 to uropods is mediated by its heparan sulfate chains and that targeting is regulated by cell surface events rather than solely by intracellular mechanisms. The addition of exogenous heparin or the treatment of polarized cells with heparitinase initiates a rapid and dramatic redistribution of uropod syndecan-1 over the entire cell surface, and a mutated syndecan-1 lacking heparan sulfate chains fails to concentrate within uropods. Interestingly, the heparan sulfate-bearing proteoglycans glypican-1 and betaglycan fail to concentrate in uropods, indicating that targeting may require heparan sulfate structural motifs unique to syndecan-1 or that the core protein of syndecan-1 participates in specific interactions that promote heparan sulfate-mediated targeting. These findings suggest functional specificity for syndecan-1 within uropods and, in addition, reveal a novel mechanism for the targeting of molecules to discrete membrane subcellular domains via heparan sulfate.


* This work was supported by National Institutes of Health Grant CA 68494 (to R. D. S.) and a grant from The Norwegian Cancer Society (to M. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pathology, Slot 517, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205. Tel.: 501-686-6413; Fax: 501-686-5168; E-mail: SandersonRalphD@uams.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.


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