| First Author | McKee KK | Year | 2012 |
| Journal | J Cell Sci | Volume | 125 |
| Issue | Pt 19 | Pages | 4609-19 |
| PubMed ID | 22767514 | Mgi Jnum | J:199683 |
| Mgi Id | MGI:5504345 | Doi | 10.1242/jcs.107995 |
| Citation | McKee KK, et al. (2012) Schwann cell myelination requires integration of laminin activities. J Cell Sci 125(Pt 19):4609-19 |
| abstractText | Laminins promote early stages of peripheral nerve myelination by assembling basement membranes (BMs) on Schwann cell surfaces, leading to activation of beta1 integrins and other receptors. The BM composition, structural bonds and ligands needed to mediate this process, however, are not well understood. Mice hypomorphic for laminin gamma1-subunit expression that assembled endoneurial BMs with reduced component density exhibited an axonal sorting defect with amyelination but normal Schwann cell proliferation, the latter unlike the null. To identify the basis for this, and to dissect participating laminin interactions, LAMC1 gene-inactivated dorsal root ganglia were treated with recombinant laminin-211 and -111 lacking different architecture-forming and receptor-binding activities, to induce myelination. Myelin-wrapping of axons by Schwann cells was found to require higher laminin concentrations than either proliferation or axonal ensheathment. Laminins that were unable to polymerize through deletions that removed critical N-terminal (LN) domains, or that lacked cell-adhesive globular (LG) domains, caused reduced BMs and almost no myelination. Laminins engineered to bind weakly to alpha6beta1 and/or alpha7beta1 integrins through their LG domains, even though they could effectively assemble BMs, decreased myelination. Proliferation depended upon both integrin binding to LG domains and polymerization. Collectively these findings reveal that laminins integrate scaffold-forming and cell-adhesion activities to assemble an endoneurial BM, with myelination and proliferation requiring additional alpha6beta1/alpha7beta1-laminin LG domain interactions, and that a high BM ligand/structural density is needed for efficient myelination. |
