tailieunhanh - Báo cáo khoa học: A pre-docking role for microtubules in insulin-stimulated glucose transporter 4 translocation

Insulin stimulates glucose uptake by inducing translocation of glucose transporter 4 (GLUT4) from intracellular resides to the plasma membrane. How GLUT4 storage vesicles are translocated from the cellular interior to the plasma membrane remains to be elucidated. | ỊFEBS Journal A pre-docking role for microtubules in insulin-stimulated glucose transporter 4 translocation Yu Chen Yan Wang Wei Ji Pingyong Xu and Tao Xu NationalKey Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing China Keywords GLUT4 intracellular transport microtubules TIRFM vesicle docking Correspondence T. Xu or P. Xu Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Fax 86 10 64867566 Tel 86 10 64888469 E-mail xutao@ or pyxu@ These authors contributed equally to this work Received 6 November 2007 revised 6 December 2007 accepted 11 December 2007 Insulin stimulates glucose uptake by inducing translocation of glucose transporter 4 GLUT4 from intracellular resides to the plasma membrane. How GLUT4 storage vesicles are translocated from the cellular interior to the plasma membrane remains to be elucidated. In the present study intracellular transport of GLUT4 storage vesicles and the kinetics of their docking at the plasma membrane were comprehensively investigated at single vesicle level in control and microtubule-disrupted 3T3-L1 adipocytes by time-lapse total internal reflection fluorescence microscopy. It is demonstrated that microtubule disruption substantially inhibited insulin-stimulated GLUT4 translocation. Detailed analysis reveals that microtubule disruption blocked the recruitment of GLUT4 storage vesicles to underneath the plasma membrane and abolished the docking of them at the plasma membrane. These data suggest that transport of GLUT4 storage vesicles to the plasma membrane takes place along microtubules and that this transport is obligatory for insulin-stimulated GLUT4 translocation. doi Blood glucose concentration is tightly and acutely regulated in mammals. The major mechanism that diminishes blood glucose when carbohydrates are ingested is insulin-stimulated increase of glucose uptake by skeletal muscle and adipocytes 1 . .