title: Microtubule network is required for insulin-induced signal transduction and actin remodeling.
abstract: Both microtubule and actin are required for insulin-induced glucose uptake. However, the roles of these two cytoskeletons and their relationship in insulin action still remain unclear. In this work, we examined the morphological change of microtubule/actin and their involvement in insulin signal transduction using rat skeletal muscle cells. Insulin rapidly led to microtubule clustering from ventral to dorsal surface of the cell. Microtubule filaments were rearranged to create space where new actin structures formed. Disruption of microtubule prevented insulin-induced actin remodeling and distal insulin signal transduction, with reduction in surface glucose transporter isoform 4 (GLUT4) and glucose uptake. Though microtubule mediated actin remodeling through PKCζ, reorganization of microtubule depended on tyrosine phosphorylation of insulin receptor, the mechanism is different from insulin-induced actin remodeling, which relied on the activity of PI3-kinase and PKCζ. We propose that microtubule network is required for insulin-induced signal transduction and actin remodeling in skeletal muscle cells.
authors.affiliation: Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Li Ka Shing Institute of Health, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors.forename: Li-Zhong
authors.initials: LZ
authors.lastname: Liu
authors.forename: Stanley C K
authors.initials: SC
authors.lastname: Cheung
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Lan
authors.forename: Stanley K S
authors.initials: SK
authors.lastname: Ho
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D000099221:Protein Kinase C zeta
chemical_list: D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D011972:Receptor, Insulin; D000099221:Protein Kinase C zeta; C495694:Slc2a4 protein, rat