Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology
1-Phosphatidylinositol 3-Kinase; ADP-Ribosylation Factors; Actins; Adenoviridae; Adipocytes; Androstadienes; Animals; Antimetabolites; Antineoplastic Agents; Bicyclo Compounds, Heterocyclic; Cell Line; Cell Membrane; Cells, Cultured; Deoxyglucose; Electroporation; Endothelin-1; Enzyme Inhibitors; GTP-Binding Protein alpha Subunits, Gq-G11; Genes, Dominant; Glucose Transporter Type 4; Heterotrimeric GTP-Binding Proteins; Insulin; Male; Mice; Monosaccharide Transport Proteins; *Muscle Proteins; Nocodazole; Protein Binding; Rats; Rats, Sprague-Dawley; *Signal Transduction; Thiazoles; Thiazolidines
Life Sciences | Medicine and Health Sciences
The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively active form of G(alpha)11 [G(alpha)11(Q209L)] in 3T3-L1 adipocytes causes recruitment of GLUT4 to the plasma membrane and stimulation of 2-deoxyglucose uptake. In contrast to the action of insulin on GLUT4, the effects of endothelin 1 and G(alpha)11 were not inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin at 100 nM. Signaling by insulin, endothelin 1, or G(alpha)11(Q209L) also mobilized cortical F-actin in cultured adipocytes. Importantly, GLUT4 translocation caused by all three agents was blocked upon disassembly of F-actin by latrunculin B, suggesting that the F-actin polymerization caused by these agents may be required for their effects on GLUT4. Remarkably, expression of a dominant inhibitory form of the actin-regulatory GTPase ARF6 [ARF6(T27N)] in cultured adipocytes selectively inhibited both F-actin formation and GLUT4 translocation in response to endothelin 1 but not insulin. These data indicate that ARF6 is a required downstream element in endothelin 1 signaling through G(alpha)11 to regulate cortical actin and GLUT4 translocation in cultured adipocytes, while insulin action involves different signaling pathways.
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Citation: Mol Cell Biol. 2001 Aug;21(15):5262-75. Link to article on publisher's site
DOI of Published Version
Molecular and cellular biology
Bose, Avirup; Cherniack, Andrew D.; Langille, Stephen E.; Nicoloro, Sarah M.; Buxton, Joanne M.; Park, Jin Gyoon; Chawla, Anil; and Czech, Michael P., "G(alpha)11 signaling through ARF6 regulates F-actin mobilization and GLUT4 glucose transporter translocation to the plasma membrane" (2001). Open Access Articles. 1433.