UMMS Affiliation

Program in Molecular Medicine; Department of Physiology

Date

6-1-2004

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; 3T3-L1 Cells; Adipocytes; Animals; Chromones; Enzyme Inhibitors; Exocytosis; Glucose Transporter Type 4; Insulin; Membrane Fusion; Mice; Molecular Motor Proteins; Monosaccharide Transport Proteins; Morpholines; *Muscle Proteins; Myosins; Recombinant Fusion Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Glucose homeostasis is controlled in part by regulation of glucose uptake into muscle and adipose tissue. Intracellular membrane vesicles containing the GLUT4 glucose transporter move towards the cell cortex in response to insulin and then fuse with the plasma membrane. Here we show that the fusion step is retarded by the inhibition of phosphatidylinositol (PI) 3-kinase. Treatment of insulin-stimulated 3T3-L1 adipocytes with the PI 3-kinase inhibitor LY294002 causes the accumulation of GLUT4-containing vesicles just beneath the cell surface. This accumulation of GLUT4-containing vesicles near the plasma membrane prior to fusion requires an intact cytoskeletal network and the unconventional myosin motor Myo1c. Remarkably, enhanced Myo1c expression under these conditions causes extensive membrane ruffling and overrides the block in membrane fusion caused by LY294002, restoring the display of GLUT4 on the cell exterior. Ultrafast microscopic analysis revealed that insulin treatment leads to the mobilization of GLUT4-containing vesicles to these regions of Myo1c-induced membrane ruffles. Thus, localized membrane remodeling driven by the Myo1c motor appears to facilitate the fusion of exocytic GLUT4-containing vesicles with the adipocyte plasma membrane.

Rights and Permissions

Citation: Mol Cell Biol. 2004 Jun;24(12):5447-58. Link to article on publisher's site

DOI of Published Version

10.1128/MCB.24.12.5447-5458.2004

Related Resources

Link to Article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID

15169906

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