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


CONCLUSIONS
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.
Heyward
Catherine A
CA
CR-UK Institute for Cancer Studies, Birmingham University, Birmingham B15 2TT, UK. c.a.heyward@liverpool.ac.uk
Pettitt
Trevor R
TR
Leney
Sophie E
SE
Welsh
Gavin I
GI
Tavaré
Jeremy M
JM
Wakelam
Michael J O
MJ
D041721:3T3-L1 Cells; D017667:Adipocytes; D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D001693:Biological Transport, Active; D022162:Cytoplasmic Vesicles / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D016296:Mutagenesis; D050505:Mutant Proteins; D009154:Mutation; D019151:Peptide Library; D014162:Transfection
D051275:Glucose Transporter Type 4; D007328:Insulin; D050505:Mutant Proteins; D019151:Peptide Library; D005947:Glucose