Evidence for a role of the exocyst in insulin-stimulated Glut4 trafficking in 3T3-L1 adipocytes

J Biol Chem. 2005 Feb 4;280(5):3812-6. doi: 10.1074/jbc.M409928200. Epub 2004 Nov 17.

Abstract

Insulin stimulates glucose transport in adipocytes and muscle by inducing the redistribution of Glut4 from intracellular locations to the plasma membrane. The fusion of Glut4-containing vesicles at the plasma membrane is known to involve the target SNAREs syntaxin 4 and SNAP-23 and the vesicle SNARE VAMP2. Little is known about the initial docking of Glut4 vesicles with the plasma membrane. A recent report has implicated Exo70, a component of the mammalian exocyst complex, in the initial interaction of Glut4 vesicles with the adipocyte plasma membrane. Here, we have examined the role of two other exocyst components, rsec6 and rsec8. We show that insulin promotes a redistribution of rsec6 and rsec8 to the plasma membrane and to cytoskeletal fractions within 3T3-L1 adipocytes but does not modulate levels of these proteins co-localized with Glut4. We further show that adenoviral-mediated overexpression of either rsec6 or rsec8 increases the magnitude of insulin-stimulated glucose transport in 3T3-L1 adipocytes. By contrast, overexpression of rsec6 or rsec8 did not increase the extent of the secretion of adipsin or ACRP30 from adipocytes and had no discernible effect on transferrin receptor traffic. Collectively, our data support a role for the exocyst in insulin-stimulated glucose transport and suggest a model by which insulin-dependent relocation of the exocyst to the plasma membrane may contribute to the specificity of Glut4 vesicle docking and fusion with the adipocyte plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism
  • Exocytosis / drug effects
  • Glucose Transporter Type 4
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Kidney / cytology
  • Membrane Proteins
  • Mice
  • Monosaccharide Transport Proteins / metabolism*
  • Muscle Proteins / metabolism*
  • Protein Transport / drug effects*
  • Rats
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Carrier Proteins
  • Exoc3 protein, rat
  • Exoc4 protein, rat
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Membrane Proteins
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Recombinant Proteins
  • SLC2A4 protein, human
  • Slc2a4 protein, mouse
  • Slc2a4 protein, rat