Heparan sulfate regulates targeting of syndecan-1 to a functional domain on the cell surface.
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 beta glycan 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.
Yang
Yang
Y
Department of Pathology, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Børset
Magne
M
Langford
J Kevin
JK
Sanderson
Ralph D
RD
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D014162:Transfection
D018076:DNA, Complementary; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; D011994:Recombinant Proteins; D053668:Syndecan-1; D053667:Syndecans; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; C508243:Sdc1 protein, rat; C021349:heparitinsulfate lyase