| First Author | Wakatsuki S | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 5 | Pages | 2957-66 |
| PubMed ID | 19049978 | Mgi Jnum | J:147216 |
| Mgi Id | MGI:3839703 | Doi | 10.1074/jbc.M803191200 |
| Citation | Wakatsuki S, et al. (2009) Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration. J Biol Chem 284(5):2957-66 |
| abstractText | Remyelination is an important aspect of nerve regeneration after nerve injury, but the underlying mechanisms are not fully understood. Here, we show that meltrin-beta (ADAM19), a member of the ADAM (a disintegrin and metalloprotease) family, plays crucial roles in nerve regeneration after a crush injury to the sciatic nerves. The expression of meltrin-beta was up-regulated in neurons after the crush injury. Morphometrical analysis revealed a delay in remyelination in meltrin-beta-deficient nerves, whereas no significant defects were observed in their axon elongation. The activation of Krox-20, an indispensable transcription factor for myelination, was delayed in meltrin-beta-deficient nerves and was accompanied by the retarded expression of myelin-related proteins. Expression of Krox-20 in Schwann cells was mediated by Akt. Phosphorylation of Akt but not that of Erks was reduced in regenerating nerves of meltrin-beta-deficient mice. The cell membrane fraction prepared from meltrin-beta-deficient nerves showed a defective activation of Akt in the membrane-loaded Schwann cells. Meltrin-beta-deficient mice exhibited delayed sciatic functional recovery after the nerve crush. Altogether, these results reveal a role of meltrin-beta in Schwann cell differentiation and re-myelination in nerve regeneration. Moreover, this study suggests that meltrin-beta functions as a modulator of juxtacrine signaling from axons that activate the Akt pathway and the Krox-20 expression, which is the prerequisite for Schwann cell differentiation. |
