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Vol. 17, Issue 5, 2303-2311, May 2006

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Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering

Mayumi Inoue ^*, Shian-Huey Chiang ^*, Louise Chang ^*, Xiao-Wei Chen ^* , and Alan R. Saltiel ^* 

^* Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109

Submitted January 13, 2006; Revised February 24, 2006; Accepted February 28, 2006
Monitoring Editor: Adam Linstedt

Lipid raft microdomains act as organizing centers for signal transduction. We report here that the exocyst complex, consisting of Exo70, Sec6, and Sec8, regulates the compartmentalization of Glut4-containing vesicles at lipid raft domains in adipocytes. Exo70 is recruited by the G protein TC10 after activation by insulin and brings with it Sec6 and Sec8. Knockdowns of these proteins block insulin-stimulated glucose uptake. Moreover, their targeting to lipid rafts is required for glucose uptake and Glut4 docking at the plasma membrane. The assembly of this complex also requires the PDZ domain protein SAP97, a member of the MAGUKs family, which binds to Sec8 upon its translocation to the lipid raft. Exocyst assembly at lipid rafts sets up targeting sites for Glut4 vesicles, which transiently associate with these microdomains upon stimulation of cells with insulin. These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Alan R. Saltiel (saltiel{at}umich.edu).

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