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Molecular and Cellular Biology, August 2001, p. 5262-5275, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.5262-5275.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Galpha 11 Signaling through ARF6 Regulates F-Actin Mobilization and GLUT4 Glucose Transporter Translocation to the Plasma Membrane

Avirup Bose, Andrew D. Cherniack, Stephen E. Langille,dagger Sarah M. C. Nicoloro, Joanne M. Buxton, Jin G. Park, Anil Chawla, and Michael P. Czech*

Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical Center, Worcester, Massachusetts 01605

Received 11 December 2000/Returned for modification 8 February 2001/Accepted 30 April 2001

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 Galpha q or Galpha 11 proteins. Here we report that murine Galpha 11 is most abundant in fat and that expression of the constitutively active form of Galpha 11 [Galpha 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 Galpha 11 were not inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin at 100 nM. Signaling by insulin, endothelin 1, or Galpha 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 Galpha 11 to regulate cortical actin and GLUT4 translocation in cultured adipocytes, while insulin action involves different signaling pathways.

* Corresponding author. Mailing address: Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Worcester, MA 01605. Phone: (508) 856-2254. Fax: (508) 856-1617. E-mail: Michael.Czech{at}umassmed.edu.

dagger Present address: Office of Generic Drugs, Food and Drug Administration, Rockville, MD 20855-2773.

Molecular and Cellular Biology, August 2001, p. 5262-5275, Vol. 21, No. 15
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.15.5262-5275.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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