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Open Access Research article

An intracellular motif of GLUT4 regulates fusion of GLUT4-containing vesicles

Catherine A Heyward1, Trevor R Pettitt1, Sophie E Leney2, Gavin I Welsh2, Jeremy M Tavaré2 and Michael JO Wakelam13*

Author Affiliations

1 CR-UK Institute for Cancer Studies, Birmingham University, Birmingham B15 2TT, UK

2 Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK

3 Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK

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BMC Cell Biology 2008, 9:25  doi:10.1186/1471-2121-9-25

Published: 20 May 2008

Abstract

Background

Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is not yet clear.

Results

Here we report the identification of a putative phosphatidic acid-binding motif in a GLUT4 intracellular loop. Mutation of this motif causes a decrease in the insulin-induced exposure of GLUT4 at the cell surface of 3T3-L1 adipocytes via an effect on vesicle fusion.

Conclusion

The potential phosphatidic acid-binding motif identified in this study is unique to GLUT4 among the sugar transporters, therefore this motif may provide a unique mechanism for regulating insulin-induced translocation by phospholipase D signalling.