Schwann Cell Adhesion to a Novel Heparan Sulfate Binding Site in the N-terminal Domain of 4 Type V Collagen Is Mediated by Syndecan-3

Sigfried and Janet Weis Center for Research, Geisinger Clinic, 100 North Academy Avenue, Danville, PA 17822, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 04/2002; 277(9):7619-25. DOI: 10.1074/jbc.M111311200
Source: PubMed


Previously we reported that type V collagen synthesized by Schwann cells inhibits the outgrowth of axons from rat embryo dorsal root ganglion neurons but promotes Schwann cell migration (Chernousov, M. A., Stahl, R. C., and Carey, D. J. (2001) J. Neurosci. 21, 6125-6135). Analysis of Schwann cell adhesion and spreading on dishes coated with various type V collagen domains revealed that Schwann cells adhered effectively only to the non-collagenous N-terminal domain (NTD) of the alpha4(V) collagen chain. Schwann cell adhesion to alpha4(V)-NTD induced actin cytoskeleton assembly, tyrosine phosphorylation, and activation of the Erk1/Erk2 protein kinases. Adhesion to alpha4(V)-NTD is cell type-specific because rat fibroblasts failed to adhere to dishes coated with this polypeptide. Schwann cell adhesion and spreading on alpha4(V)-NTD was strongly inhibited by soluble heparin (IC(50) approximately 30 ng/ml) but not by chondroitin sulfate. Analysis of the heparin binding activities of a series of recombinant alpha4(V)-NTD fragments and deletion mutants identified a highly basic region (not present in other type V collagen NTD) as the site responsible for high affinity heparin binding. Schwann cells adhered poorly to dishes coated with alpha4(V)-NTD that lacked the heparin binding site and failed to spread or assemble organized actin-cytoskeletal structures. Soluble alpha4(V)-NTD polypeptide that contained the heparin binding site inhibited spreading of Schwann cells on dishes coated with alpha4(V)-NTD. Affinity chromatography of Schwann cell detergent extracts on a column of immobilized alpha4(V)-NTD resulted in the isolation of syndecan-3, a transmembrane heparan sulfate proteoglycan. Together, these results suggest that Schwann cells bind to collagen type V via syndecan-3-dependent binding to a novel high affinity heparin binding site in the alpha4(V)-NTD.

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    • "Studies of collagen type V show an influence on cell behavior. The Nterminal domain of Col5a4 has been found to modulate Schwann cell migration by utilizing syndecan-3 (Erdman et al., 2002), which is a transmembrane heparan sulfate proteoglycan. Although not specified as to which alpha chain or which domain is involved, Luparello and colleagues demonstrated that type V collagen can induce apoptosis in a cell line-dependent manner (Pucci-Minafra et al., 2000; Luparello and Sirchia, 2005). "
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    • "Exon 6 (E6) in Col5a1 and E6A, E8 in Col11a1 as well as E8 in Col11a2 are rich in tyrosine and acidic residues aspartic acid and glutamic acid; whereas E6 in Col5a3 and E6B in Col11a1 include clusters of arginines and lysines. Tyrosine of Col5a1 is known to be extensively sulfonated in the extracellular matrix, and successive arginines and lysines have been shown to serve as a binding motif for proteoglycans (Erdman et al, 2002; Yamaguchi et al, 2005). "
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