THE ROLE OF G2L1 IN MICROTUBULE AND ACTIN-BASED INSULIN-STIMULATED DELIVERY OF GLUCOSE TRANSPORTER 4 TO THE PLASMA MEMBRANE
PublisherThe University of Arizona.
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AbstractInsulin-stimulated glucose uptake, a key physiological system, is known to be directly influenced by microtubule action through insulin-stimulated glucose transporter 4 (GLUT4) vesicle trafficking. GLUT4 vesicles move along microtubules towards the plasma membrane and upon reaching the cell periphery, microtubules are hypothesized to crosslink with branched actin on the inner surface of the plasma membrane. This cytoskeletal interaction is proposed to transition GLUT4 for fusion with the cell surface, ultimately leading to insulin stimulated glucose transport into the cell. However, the molecular mechanism of microtubule-based GLUT4 delivery to actin-enriched regions on the plasma membrane has not been discovered. Previously, we identified an insulin responsive protein network in 3T3-L1 adipocytes centered around CLASP2, a microtubule-associated protein (MAP) we discovered to be involved in insulin action. Characterization of the CLASP2 protein network led us to discover other MAPs which may be key players in glucose uptake, including the actin and microtubule binding protein G2L1. Based on our discovery that insulin affects G2L1 localization and phosphorylation, we hypothesize that G2L1, through cytoskeletal and protein interactions, coordinates microtubule and actin-based delivery of GLUT4 to the cell periphery. With this in mind, we set out to study the effects of G2L1 knockdown in our cell model, differentiated 3T3-L1 adipocytes, to assess whether G2L1 knockdown affects GLUT4 trafficking and insulin-stimulated glucose transport.
Degree ProgramMolecular and Cellular Biology