HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 51, 39719-39727, December 22, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/51/39719    most recent M607101200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eyster, C. A. Articles by Olson, A. L. Search for Related Content PubMed PubMed Citation Articles by Eyster, C. A. Articles by Olson, A. L. Social Bookmarking                      What's this?

Microtubule Network Is Required for Insulin Signaling through Activation of Akt/Protein Kinase B

EVIDENCE THAT INSULIN STIMULATES VESICLE DOCKING/FUSION BUT NOT INTRACELLULAR MOBILITY^*

Craig A. Eyster, Quwanza S. Duggins, Gary J. Gorbsky, and Ann Louise Olson¹

From the Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104 and the Oklahoma Medical Research Foundation and Department of Cell Biology, Health Science Center, Oklahoma University, Oklahoma City, Oklahoma 73104

The microtubule network has been shown to be required for insulin-dependent GLUT4 redistribution; however, the precise molecular function has not been elucidated. In this article, we used fluorescence recovery after photobleaching (FRAP) to evaluate the role of microtubules in intracellular GLUT4 vesicle mobility. A comparison of the rate of fluorescence recovery (t), and the maximum fluorescence recovered (F_max) was made between basal and insulin-treated cells with or without nocodazole treatment to disrupt microtubules. We found that intracellular mobility of fluorescently tagged GLUT4 (HA-GLUT4-GFP) was high in basal cells. Mobility was not increased by insulin treatment. Basal mobility was dependent upon an intact microtubule network. Using a constitutively active Akt to signal GLUT4 redistribution, we found that microtubule-based GLUT4 vesicle mobility was not obligatory for GLUT4 plasma membrane insertion. Our findings suggest that microtubules organize the insulin-signaling complex and provide a surface for basal mobility of GLUT4 vesicles. Our data do not support an obligatory requirement for long range microtubule-based movement of GLUT4 vesicles for insulin-mediated GLUT4 redistribution to the cell surface. Taken together, these findings suggest a model in which insulin signaling targets membrane docking and/or fusion rather than GLUT4 trafficking to the cell surface.

Received for publication, July 26, 2006 , and in revised form, October 4, 2006.

^* This work was supported in part by National Institutes of Health Grants DK68438 and DK62341 (to A. L. O.) and GM50412 (to G. J. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3 and Movies M1-M8.

¹ To whom correspondence should be addressed: OUHSC, Dept. of Biochemistry and Molecular Biology, P.O. Box 26901, Rm 853 BMSB. Tel.: 405-271-2227; Fax: 405-271-3092; E-mail: ann-olson{at}ouhsc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Jiang, H. Kenerson, L. Aicher, R. Miyaoka, J. Eary, J. Bissler, and R. S. Yeung The Tuberous Sclerosis Complex Regulates Trafficking of Glucose Transporters and Glucose Uptake Am. J. Pathol., June 1, 2008; 172(6): 1748 - 1756. [Abstract] [Full Text] [PDF]

				C. Montessuit, I. Papageorgiou, and R. Lerch Nuclear Receptor Agonists Improve Insulin Responsiveness in Cultured Cardiomyocytes through Enhanced Signaling and Preserved Cytoskeletal Architecture Endocrinology, March 1, 2008; 149(3): 1064 - 1074. [Abstract] [Full Text] [PDF]