Signaling from Integrins to Fyn to Rho Family GTPases Regulates Morphologic Differentiation of Oligodendrocytes

• DOI: 10.1523/jneurosci.5319-03.2004
• Publication Date: 2004-08-11T18:27:34Z
• Authors: Xiquan Liang; Nicole A. Draghi; Marilyn D. Resh
• Keywords: FYN; CDC42

Differentiation of oligodendrocyte progenitor cells requires activation the Src family kinase Fyn. The signals that are upstream and downstream Fyn in oligodendrocytes remain essentially unknown. Here we show extracellular matrix engagement regulates morphology activates Infection primary cultures with recombinant adenovirus revealed expression or its target p190RhoGAP induced process extension. This phenotypic change was not observed when kinase-inactive GAP-defective p190 mutants were expressed. Because Rho proteins regulated by p190, monitored effects introducing dominant-negative (DN) constitutively activated (CA) versions Rho, Rac1, Cdc42 into cultures. Expression DN CA outgrowth processes, whereas introduction cdc42 inhibited differentiation, indicating Cdc42-Rac1 exert opposing on differentiation. Direct measurement activity RhoA downregulated, Rac1 upregulated during differentiation oligodendrocytes. Moreover, inhibition integrin blocked as well myelin basic protein expression. Taken together, these results suggest a linear signal transduction pathway integrin-Fyn-Rho GTPases controls morphologic