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Publication : Phosphorylation of cytohesin-1 by Fyn is required for initiation of myelination and the extent of myelination during development.

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.
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