| First Author | Chun SJ | Year | 2003 |
| Journal | J Cell Biol | Volume | 163 |
| Issue | 2 | Pages | 397-408 |
| PubMed ID | 14581460 | Mgi Jnum | J:86333 |
| Mgi Id | MGI:2679417 | Doi | 10.1083/jcb.200304154 |
| Citation | Chun SJ, et al. (2003) Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. J Cell Biol 163(2):397-408 |
| abstractText | Early steps in myelination in the central nervous system (CNS) include a specialized and extreme form of cell spreading in which oligodendrocytes extend large lamellae that spiral around axons to form myelin. Recent studies have demonstrated that laminin-2 (LN-2; alpha2beta1gamma1) stimulates oligodendrocytes to extend elaborate membrane sheets in vitro (cell spreading), mediated by integrin alpha6beta1. Although a congenital LN-2 deficiency in humans is associated with CNS white matter changes, LN-2-deficient (dy/dy) mice have shown abnormalities primarily within the peripheral nervous system. Here, we demonstrate a critical role for LN-2 in CNS myelination by showing that dy/dy mice have quantitative and morphologic defects in CNS myelin. We have defined the molecular pathway through which LN-2 signals oligodendrocyte cell spreading by demonstrating requirements for phosphoinositide 3-kinase activity and integrin-linked kinase (ILK). Interaction of oligodendrocytes with LN-2 stimulates ILK activity. A dominant negative ILK inhibits LN-2-induced myelinlike membrane formation. A critical component of the myelination signaling cascade includes LN-2 and integrin signals through ILK. |
