Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation.
Phosphatidylinositol-3-phosphate (PtdIns-3-P) is considered as a lipid constitutively present on endosomes; it does not seem to have a dynamic role in signalling. In contrast, phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P(3)) plays a crucial role in different signalling pathways including translocation of the glucose transporter protein GLUT4 to the plasma membrane upon insulin receptor activation. GLUT4 translocation requires activation of two distinct pathways involving phosphatidylinositol 3-kinase (PI 3-K) and the small GTP-binding protein TC10, respectively. The contribution of each pathway remains to be elucidated. Here we show that insulin specifically induces the formation of PtdIns-3-P in insulin- responsive cells. The insulin-mediated formation of PtdIns-3-P occurs through the activation of TC10 at the lipid rafts subdomain of the plasma membrane. Exogenous PtdIns-3-P induces the plasma membrane translocation of both overexpressed and endogenous GLUT4. These data indicate that PtdIns-3-P is specifically produced downstream from insulin-mediated activation of TC10 to promote the plasma membrane translocation of GLUT4. These results give a new insight into the intracellular role of PtdIns-3-P and shed light on some aspects of insulin signalling so far not completely understood.
Maffucci
Tania
T
The Sackler Institute, University College London, 5 University Street, London WC1E 6JJ, UK.
Brancaccio
Anna
A
Piccolo
Enza
E
Stein
Robert C
RC
Falasca
Marco
M
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009124:Muscle Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015290:Second Messenger Systems; D000077191:Wortmannin; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009025:Morpholines; D009124:Muscle Proteins; D018129:Phosphatidylinositol Phosphates; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; C495693:Slc2a4 protein, mouse; C055525:phosphatidylinositol 3-phosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; C503260:Rhoq protein, mouse; D020741:rho GTP-Binding Proteins; D000077191:Wortmannin