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

Abstract

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.

A Novel Mechanism of Sequestering Fibroblast Growth Factor 2 by Glypican in Lipid Rafts, Allowing Skeletal Muscle Differentiation

“…A FLAG epitope in the amino terminal of extracellular domain was incorporated into a chimeric HSPG containing the extracellular domain of rat glypican-1 and the cytoplasmatic domain of mouse syndecan-1 (GlySyn) (45,85) Isolation of lipid rafts. Lipid rafts were prepared as described previously (90), with some modifications.…”

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“…The survival of MM cells is dependent on the growth conditions provided by the bone marrow microenvironment. PGs such as syndecan-1, present on myeloma cell surface but also shed in extracellular matrix (22), are important for myeloma cell biology and bone homeostasis (23)(24)(25)(26)(27)(28).…”

FGF2 binding, signaling and angiogenesis are modulated by heparanase in metastatic melanoma cells

“…This has been demonstrated with the HSPG syndecan-1 [52] and glypican [53], whose localization in the plasma membrane is affected by removing HS or by inhibiting HS interactions.…”