Laminin-sulfatide binding initiates basement membrane assembly and enables receptor signaling in Schwann cells and fibroblasts.
Endoneurial laminins (Lms), beta1-integrins, and dystroglycan (DG) are important for Schwann cell (SC) ensheathment and myelination of axons. We now show that SC expression of galactosyl-sulfatide, a Lm-binding glycolipid, precedes that of Lms in developing nerves. This glycolipid anchors Lm-1 and -2 to SC surfaces by binding to their LG domains and enables basement membrane (BM) assembly. Revealingly, non-BM-forming fibroblasts become competent for BM assembly when sulfatides are intercalated into their cell surfaces. Assembly is characterized by coalescence of sulfatide, DG, and c-Src into a Lm-associated complex; by DG-dependent recruitment of utrophin and Src activation; and by integrin-dependent focal adhesion kinase phosphorylation. Collectively, our findings suggest that sulfated glycolipids are key Lm anchors that determine which cell surfaces can assemble Lms to initiate BM assembly and DG- and integrin-mediated signaling.
Li
Shaohua
S
Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Liquari
Patricia
P
McKee
Karen K
KK
Harrison
David
D
Patel
Raj
R
Lee
Sean
S
Yurchenco
Peter D
PD
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002478:Cells, Cultured; D049030:Dystroglycans / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D051418:Focal Adhesion Kinase 2; D016391:Genes, src / Q000502:physiology; D006017:Glycolipids / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D049411:Utrophin / Q000378:metabolism
D051242:Caveolin 1; D022461:Caveolins; D006017:Glycolipids; D016023:Integrins; D007797:Laminin; D013433:Sulfoglycosphingolipids; D049411:Utrophin; D049030:Dystroglycans; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2