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The Journal of Neuroscience, May 15, 2000, 20(10):3776-3784

Association of 1 Integrin with Focal Adhesion Kinase and Paxillin in Differentiating Schwann Cells

Li-Mei Chen, Debora Bailey, and Cristina Fernandez-Valle

Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida 32816-2360, and Orlando Regional Healthcare System/Health Research Institute, Orlando, Florida 32806

Schwann cells (SCs) differentiate into a myelinating cell when simultaneously adhering to an axon destined for myelination and basal lamina. We are interested in defining the signaling pathway activated by basal lamina. Using SC/sensory neuron (N) cocultures, we identified 1 integrin and F-actin as components of a pathway leading to myelin gene expression and myelination (Fernandez-Valle et al., 1994, 1997). Here, we show that focal adhesion kinase (FAK) and paxillin are constitutively expressed by SCs contacting axons in the absence of basal lamina. Tyrosine phosphorylation of FAK and paxillin increases as SCs form basal lamina and differentiate. FAK and paxillin specifically coimmunoprecipitate with 1 integrin in differentiating SC/N cocultures but not SC-only cultures. Paxillin coimmunoprecipitates with FAK and fyn kinase in differentiating SC/N cocultures. A subset of tyrosine-phosphorylated 1 integrin, FAK, and paxillin molecules reside in the insoluble, F-actin-rich fraction of differentiating cocultures. Cytochalasin D, an actin depolymerizing agent, decreases tyrosine phosphorylation of FAK and paxillin and their association with 1 integrin and causes a dose-dependent increase in the abundance of insoluble FAK and paxillin complexes. Collectively, our work indicates that 1 integrin, FAK, paxillin, and fyn kinase form an actin-associated complex in SCs adhering to basal lamina in the presence of axons. This complex may be important for initiating the process of SC differentiation into a myelinating cell.

Key words: Schwann cells; myelination; basal lamina; 1 integrin; focal adhesion kinase; paxillin; tyrosine phosphorylation; signal transduction

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20103776-09$05.00/0

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