Schwann cell adhesion to a novel heparan sulfate binding site in the N-terminal domain of alpha 4 type V collagen is mediated by syndecan-3.
ABSTRACT 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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ABSTRACT: Laminins and collagens are extracellular matrix proteins that play essential roles in peripheral nervous system de- velopment. Laminin signals regulate Schwann cell prolifer- ation and survival as well as actin cytoskeleton dynamics, which are essential steps for radial sorting and myelination of peripheral axons by Schwann cells. Collagen and their receptors promote Schwann cell adhesion, spreading, and myelination as well as neurite outgrowth. In this article, we will review the recent advances in the studies of laminin and collagen function in Schwann cell develop- ment. V V C 2008 Wiley-Liss, Inc.
- Methods in Microbiology - METH MICROBIOL. 01/1998; 27:455-464.
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ABSTRACT: In the peripheral nervous system, myelin is formed by Schwann cells, which are surrounded by a basal lamina. Extracellular matrix (ECM) molecules in the basal lamina play an important role in regulating Schwann cell functions, including adhesion, survival, spreading, and myelination, as well as in supporting neurite outgrowth. Collagens are a major component of ECM molecules, which include 28 types that differ in structure and function. A growing body of evidence suggests that collagens are key components of peripheral nerves, where they not only provide a structural support but also affect cell behavior by triggering intracellular signals. In this review, we will summarize the main properties of collagen family, discuss the role of extensively studied collagen types (collagens IV, V, VI, and XV) in Schwann cell function and myelination, and provide a detailed overview of the recent advances with respect to these collagens in peripheral nerve function.Molecular neurobiology. 08/2014;