title: Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking.
abstract: The Rab-GTPase-activating proteins (GAPs) TBC1D1 and TBC1D4 play important roles in the insulin-stimulated translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane in muscle cells and adipocytes. We identified Rab28 as a substrate for the GAP domains of both TBC1D1 and TBC1D4 in vitro. Rab28 is expressed in adipose cells and skeletal muscle, and its GTP-binding state is acutely regulated by insulin. We found that in intact isolated mouse skeletal muscle, siRNA-mediated knockdown of Rab28 decreases basal glucose uptake. Conversely, in primary rat adipose cells, overexpression of Rab28-Q72L, a constitutively active mutant, increases basal cell surface levels of an epitope-tagged HA-GLUT4. Our results indicate that Rab28 is a novel GTPase involved in the intracellular retention of GLUT4 in insulin target cells.
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München, Neuherberg, Germany.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Menzel
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München, Neuherberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Benninghoff
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München, Neuherberg, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chadt
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Chen
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Holman
authors.affiliation: Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München, Neuherberg, Germany.
authors.forename: Hadi
authors.initials: H
authors.lastname: Al-Hasani
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D000072417:Protein Domains; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity / Q000187:drug effects; D014316:Tritium / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C095906:Tbc1d1 protein, mouse; C505647:Tbc1d4 protein, mouse; D014316:Tritium; D006160:Guanosine Triphosphate; D003847:Deoxyglucose; C503252:Rab28 protein, mouse; D020691:rab GTP-Binding Proteins
keywords: GLUT4; GTPase; adipose tissue; insulin signaling; skeletal muscle