RESUMO

Insulin stimulates glucose uptake in muscle cells by rapidly redistributing vesicles containing GLUT4 glucose transporters from intracellular compartments to the plasma membrane (PM). GLUT4 vesicle fusion requires the formation of SNARE complexes between vesicular VAMP and PM syntaxin4 and SNAP23. SNARE accessory proteins usually regulate vesicle fusion processes. Complexins aide in neuro-secretory vesicle-membrane fusion by stabilizing trans-SNARE complexes but their participation in GLUT4 vesicle fusion is unknown. We report that complexin-2 is expressed and homogeneously distributed in L6 rat skeletal muscle cells. Upon insulin stimulation, a cohort of complexin-2 redistributes to the PM. Complexin-2 knockdown markedly inhibited GLUT4 translocation without affecting proximal insulin signalling of Akt/PKB phosphorylation and actin fiber remodelling. Similarly, complexin-2 overexpression decreased maximal GLUT4 translocation suggesting that the concentration of complexin-2 is finely tuned to vesicle fusion. These findings reveal an insulin-dependent regulation of GLUT4 insertion into the PM involving complexin-2.

Assuntos

Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/farmacologia , Mioblastos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Transportador de Glucose Tipo 4/genética , Insulina/genética , Insulina/metabolismo , Músculo Esquelético/citologia , Mioblastos/efeitos dos fármacos , Proteínas do Tecido Nervoso/genética , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo