title: Glypican-1 and alpha4(V) collagen are required for Schwann cell myelination.
abstract: Schwann cell myelination requires interactions with the extracellular matrix (ECM) mediated by cell surface receptors. Previously, we identified a type V collagen family member, alpha4(V) collagen, which is expressed by Schwann cells during peripheral nerve differentiation. This collagen binds with high affinity to heparan sulfate through a unique binding motif in the noncollagenous N-terminal domain (NTD). The principal alpha4(V) collagen-binding protein on the Schwann cell surface is the heparan sulfate proteoglycan glypican-1. We investigated the role of alpha4(V) collagen and glypican-1 in Schwann cell terminal differentiation in cultures of Schwann cells and dorsal root ganglion neurons. Small interfering RNA-mediated suppression of glypican-1 expression decreased binding of alpha4(V)-NTD to Schwann cells, adhesion and spreading of Schwann cells on alpha4(V)-NTD, and incorporation of alpha4(V) collagen into Schwann cell ECM. In cocultures, alpha4(V) collagen coassembles with laminin on the surface of polarized Schwann cells to form tube-like ECM structures that are sites of myelination. Suppression of glypican-1 or alpha4(V) collagen expression significantly inhibited myelination. These results demonstrate an important role for these proteins in peripheral nerve terminal differentiation.
authors.affiliation: Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2601, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Chernousov
authors.forename: Katrina
authors.initials: K
authors.lastname: Rothblum
authors.forename: Richard C
authors.initials: RC
authors.lastname: Stahl
authors.forename: Ann
authors.initials: A
authors.lastname: Evans
authors.forename: Lisa
authors.initials: L
authors.lastname: Prentiss
authors.forename: David J
authors.initials: DJ
authors.lastname: Carey
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000166:cytology; D018920:Coculture Techniques; D024062:Collagen Type V / Q000235:genetics / Q000502:physiology*; D016895:Culture Media, Serum-Free; D005109:Extracellular Matrix; D005727:Ganglia, Spinal / Q000166:cytology; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology; D014162:Transfection
chemical_list: D024062:Collagen Type V; D016895:Culture Media, Serum-Free; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins