title: An actin filament population defined by the tropomyosin Tpm3.1 regulates glucose uptake.
abstract: Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM.
authors.affiliation: Cellular and Genetic Medicine Unit, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kee
authors.affiliation: Cellular and Genetic Medicine Unit, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Cellular and Genetic Medicine Unit, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Lucas
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6085, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Greenberg
authors.affiliation: Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Martel
authors.affiliation: Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.|Department of Paediatric Endocrinology and Diabetes, Mater Children's Hospital, South Brisbane, QLD, 4010, Australia.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Leong
authors.affiliation: Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
authors.forename: William E
authors.initials: WE
authors.lastname: Hughes
authors.affiliation: Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cooney
authors.affiliation: Charles Perkins Centre, School of Molecular Bioscience, University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.affiliation: The Pennsylvania Muscle Institute and Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104-6085, USA.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Ostap
authors.affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore, 138667, Singapore.
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.affiliation: Oncology Research Unit, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
authors.affiliation: Cellular and Genetic Medicine Unit, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D024461:Myosin Type I / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; C411923:Tpm3 protein, mouse; D014335:Tropomyosin; D024461:Myosin Type I; D005947:Glucose
keywords: GLUT4; actin cytoskeleton; glucose uptake; myosins; tropomyosin