First Author | Yamauchi J | Year | 2012 |
Journal | Sci Signal | Volume | 5 |
Issue | 243 | Pages | ra69 |
PubMed ID | 23012656 | Mgi Jnum | J:259473 |
Mgi Id | MGI:6142815 | Doi | 10.1126/scisignal.2002802 |
Citation | Yamauchi J, et al. (2012) Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development. Sci Signal 5(243):ra69 |
abstractText | Schwann cells respond to cues from axons by transforming their cellular morphology and forming myelin. We demonstrated that the guanine nucleotide exchange factor (GEF) cytohesin-1 promoted myelination by activating the small guanosine triphosphatase (GTPase) Arf6. In mice, ablating cytohesin-1 delayed myelination and diminished the amount of myelin produced. We determined that the Src-family kinase Fyn phosphorylated tyrosine 382 (Y(382)) of cytohesin-1, and we generated transgenic mice that expressed a Schwann cell-specific phosphorylation mutant of cytohesin-1 (Y382F) that could not be targeted by Fyn. During development, these transgenic mice displayed delayed myelination compared to that of wild-type mice, as well as a decrease in the amount of myelin produced, similar to that observed in cytohesin-1(-)/(-) mice. These findings demonstrate that phosphorylation of cytohesin-1 by Fyn is required for full myelination and suggest that tyrosine phosphorylation of GEFs may be a mechanism to activate small GTPases engaged in cell morphogenesis. |