title: Role of RalA downstream of Rac1 in insulin-dependent glucose uptake in muscle cells.
abstract: The small GTPase RalA has been implicated in glucose uptake in insulin-stimulated adipocytes, although it remains unclear whether RalA has a similar role in insulin signaling in other types of cells. Recently, we have demonstrated that the Rho family GTPase Rac1 has a critical role in insulin-dependent glucose uptake in myoblast culture and mouse skeletal muscle. However, the mechanisms underlying Rac1-dependent glucose uptake, mostly mediated by the plasma membrane translocation of the glucose transporter GLUT4, remain largely unknown. The purpose of this study is to examine the involvement of RalA in Rac1 regulation of the translocation of GLUT4 to the plasma membrane in muscle cells. Ectopic expression of a constitutively activated RalA mutant indeed stimulated GLUT4 translocation, suggesting an important role of RalA also in muscle cells. GLUT4 translocation induced by constitutively activated mutation of Rac1 or more physiologically by upstream Rac1 regulators, such as phosphoinositide 3 kinase and the guanine nucleotide exchange factor FLJ00068, was abrogated when the expression of RalA was downregulated by RNA interference. The expression of constitutively activated Rac1, on the other hand, caused GTP loading and subcellular redistribution of RalA. Collectively, we propose a novel mechanism involving RalA for Rac1-mediated GLUT4 translocation in skeletal muscle cells.
authors: Division of Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
authors: Shinsuke
authors: S
authors: Nozaki
authors: Shuji
authors: S
authors: Ueda
authors: Nobuyuki
authors: N
authors: Takenaka
authors: Tohru
authors: T
authors: Kataoka
authors: Takaya
authors: T
authors: Satoh
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D034741:RNA, Small Interfering; D019869:Phosphatidylinositol 3-Kinases; C492197:Rala protein, rat; D020830:rac1 GTP-Binding Protein; D020725:ral GTP-Binding Proteins; D005947:Glucose