Recent studies indicate that insulin stimulation of glucose transporter (GLUT)4 translocation requires at least two distinct insulin receptor–mediated signals: one leading to the activation of phosphatidylinositol 3 (PI-3) kinase and the other to the activation of the small GTP binding protein TC10. We now demonstrate that TC10 is processed through the secretory membrane trafficking system and localizes to caveolin-enriched lipid raft microdomains. Although insulin activated the wild-type TC10 protein and a TC10/H-Ras chimera that were targeted to lipid raft microdomains, it was unable to activate a TC10/K-Ras chimera that was directed to the nonlipid raft domains. Similarly, only the lipid raft–localized TC10/ H-Ras chimera inhibited GLUT4 translocation, whereas the TC10/K-Ras chimera showed no significant inhibitory activity. Furthermore, disruption of lipid raft microdomains by expression of a dominant-interfering caveolin 3 mutant (Cav3/DGV) inhibited the insulin stimulation of GLUT4 translocation and TC10 lipid raft localization and activation without affecting PI-3 kinase signaling. These data demonstrate that the insulin stimulation of GLUT4 translocation in adipocytes requires the spatial separation and distinct compartmentalization of the PI-3 kinase and TC10 signaling pathways.
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20 August 2001
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August 13 2001
Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation
Robert T. Watson,
Robert T. Watson
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
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Satoshi Shigematsu,
Satoshi Shigematsu
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
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Shian-Huey Chiang,
Shian-Huey Chiang
2Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109
3Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109
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Silvia Mora,
Silvia Mora
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
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Makoto Kanzaki,
Makoto Kanzaki
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
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Ian G. Macara,
Ian G. Macara
4Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908
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Alan R. Saltiel,
Alan R. Saltiel
3Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109
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Jeffrey E. Pessin
Jeffrey E. Pessin
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
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Robert T. Watson
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Satoshi Shigematsu
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Shian-Huey Chiang
2Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109
3Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109
Silvia Mora
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Makoto Kanzaki
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Ian G. Macara
4Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908
Alan R. Saltiel
3Departments of Internal Medicine and Physiology, Life Sciences Institute, University of Michigan Medical Center, Ann Arbor, MI 48109
Jeffrey E. Pessin
1Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Address correspondence to Jeffrey E. Pessin, Department of Physiology and Biophysics, University of Iowa, Iowa City, IA 52242. Tel.: (319) 335-7823. Fax: (319) 335-7886. E-mail: [email protected]
*
Abbreviations used in this paper: BFA, brefeldin A; CAP, Cbl-associated protein; GLUT, glucose transporter; HA, hemagglutinin; PI-3, phosphatidylinositol 3; TfR, transferrin receptor.
Received:
February 15 2001
Revision Received:
July 11 2001
Accepted:
July 12 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2001
J Cell Biol (2001) 154 (4): 829–840.
Article history
Received:
February 15 2001
Revision Received:
July 11 2001
Accepted:
July 12 2001
Citation
Robert T. Watson, Satoshi Shigematsu, Shian-Huey Chiang, Silvia Mora, Makoto Kanzaki, Ian G. Macara, Alan R. Saltiel, Jeffrey E. Pessin; Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation . J Cell Biol 20 August 2001; 154 (4): 829–840. doi: https://doi.org/10.1083/jcb.200102078
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