title: Sulfatide-mediated control of extracellular matrix-dependent oligodendrocyte maturation.
abstract: In the central nervous system, the extracellular matrix (ECM) compound laminin-2, present on developing axons, is essential in regulating oligodendrocyte (OLG) maturation. For example, laminin-2 is involved in mediating interactions between integrins and growth factors, initially localizing in separate membrane microdomains. The galactosphingolipid sulfatide is an important constituent of these microdomains and may serve as a receptor for laminin-2. Here, we investigated whether sulfatide interferes with ECM-integrin interactions and, in this manner, modulates OLG maturation. Our data reveal that disruption of laminin-2-sulfatide interactions impeded OLG differentiation and myelin-like membrane formation. On laminin-2, but not on (re)myelination-inhibiting fibronectin, sulfatide laterally associated with integrin α6 in membrane microdomains. Sulfatide was partly excluded from membrane microdomains on fibronectin, thereby likely precluding laminin-2-mediated myelination. Anti-sulfatide antibodies disrupted integrin α6-PDGFαR interactions on laminin-2 and induced demyelination in myelinated spheroid cultures, but intriguingly stimulated myelin-like membrane formation on fibronectin. Taken together, these findings highlight the importance of laminin-sulfatide interactions in the formation of functional membrane microdomains essential for myelination. Thus, laminin-sulfatide interactions might control the asynchronous localized differentiation of OLGs, thereby allowing myelination to be triggered by axonal demand. Given the accumulation of fibronectin in multiple sclerosis lesions, the findings also provide a molecular rationale for the potential of anti-sulfatide antibodies to trigger quiescent endogenous OLG progenitor cells in axon remyelination. GLIA 2014;62:927-942.
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
authors.forename: Marjolein
authors.initials: M
authors.lastname: Bijlard
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.forename: Jenny C
authors.initials: JC
authors.lastname: de Jonge
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D007797:Laminin / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009836:Oligodendroglia; D051381:Rats; D017208:Rats, Wistar; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
chemical_list: D007797:Laminin; D013433:Sulfoglycosphingolipids
keywords: fibronectin; integrin α6β1; laminin; myelination; oligodendrocyte; sulfatide