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Skeletal Muscle Cells and Adipocytes Differ in Their Reliance on TC10 and Rac for Insulin-Induced Actin Remodeling

Programme in Cell Biology (L.J., A.R., X.H., A.K.), The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8; Department of Biochemistry (L.J.) and Institute of Medical Science (C.D.C.-O., A.K.), University of Toronto, Ontario, Canada M5S 1A8; and Department of Surgery (C.D.C.-O., A.K.), Toronto General Hospital, Ontario, Canada M5G 2C4

Address all correspondence and requests for reprints to: Amira Klip, Ph.D., Programme in Cell Biology, Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: amira{at}sickkids.ca.

Insulin causes distinct cortical actin remodeling in muscle and fat cells, and interfering with actin dynamics halts glucose transporter 4 (GLUT4) translocation to the membrane. Phosphatidylinositol 3-kinase (PI3-K) and the small G protein Rac govern myocyte actin remodeling, whereas TC10 contributes to adipocyte actin dynamics downstream of Cbl-associated protein (CAP) and Cbl, independently of PI3-K. Given the importance of insulin action in both cell types, it is paramount to determine whether signaling pathways and actin manifestations are cell type specific. We found CAP expression and insulin-mediated Cbl phosphorylation in differentiated myotubes but not in myoblasts. Unlike adipocytes, Cbl is phosphorylated on Y774 and Y731 in myotubes. TC10 and ß-transcripts are amplified by RT-PCR in muscle cells, but the endogenous proteins are barely detectable using two unrelated antibodies. TC10 transfected into myoblasts is activated by insulin despite the lack of CAP expression and Cbl phosphorylation. Moreover, dominant-negative TC10 mutants do not prevent insulin-induced actin remodeling in either myoblasts or myotubes and do not interfere with insulin-mediated recruitment of c-myc epitope-tagged GLUT4 to the cell surface. In contrast to TC10, endogenous Rac is readily detectable in both muscle cells and adipocytes and binds GTP after insulin in a PI3-K-dependent manner. These data suggest that whereas individual components of the CAP to TC10 pathway are regulated by insulin, a functional TC10-dependent signaling pathway leading to actin remodeling and GLUT4 translocation may not operate in myocytes, as it does in adipocytes.

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