Compartmentalization of the Exocyst Complex in Lipid Rafts Controls Glut4 Vesicle Tethering
Open Access
- 1 May 2006
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 17 (5) , 2303-2311
- https://doi.org/10.1091/mbc.e06-01-0030
Abstract
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.Keywords
This publication has 54 references indexed in Scilit:
- Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissueAmerican Journal of Physiology-Cell Physiology, 2003
- The Adipocyte Plasma Membrane Caveolin Functional/Structural Organization Is Necessary for the Efficient Endocytosis of GLUT4Journal of Biological Chemistry, 2003
- The Vesicle- and Target-SNARE Proteins That Mediate Glut4 Vesicle Fusion Are Localized in Detergent-insoluble Lipid Rafts Present on Distinct Intracellular MembranesJournal of Biological Chemistry, 2002
- Cloning and Functional Characterization of Related TC10 Isoforms, a Subfamily of Rho Proteins Involved in Insulin-stimulated Glucose TransportPublished by Elsevier ,2002
- Insulin induces translocation of glucose transporter GLUT4 to plasma membrane caveolae in adipocytesThe FASEB Journal, 2001
- Insulin signalling and the regulation of glucose and lipid metabolismNature, 2001
- Subcellular Compartmentalization and Trafficking of the Insulin-Responsive Glucose Transporter, GLUT4Experimental Cell Research, 2001
- Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocationThe Journal of cell biology, 2001
- Cholesterol Depletion Disrupts Caveolae and Insulin Receptor Signaling for Metabolic Control via Insulin Receptor Substrate-1, but Not for Mitogen-activated Protein Kinase ControlJournal of Biological Chemistry, 2001
- Crowded Little CavesCellular Signalling, 1998