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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.
G
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,
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 G
q or
G
11 proteins. Here we report that murine
G
11 is most abundant in fat and that expression of the
constitutively active form of G
11
[G
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
11 were not inhibited by the
phosphatidylinositol 3-kinase inhibitor wortmannin at 100 nM. Signaling
by insulin, endothelin 1, or G
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
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.

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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