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

J Biol Chem. 2006 Dec 22;281(51):39719-27. doi: 10.1074/jbc.M607101200. Epub 2006 Oct 26.

Abstract

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((1/2))), 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Animals
  • Antineoplastic Agents / metabolism
  • Cell Membrane / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Glucose Transporter Type 4 / physiology*
  • Insulin / metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Microtubules / metabolism*
  • Nocodazole / pharmacology
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Glucose Transporter Type 4
  • Insulin
  • Slc2a4 protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Nocodazole