title: A potential link between insulin signaling and GLUT4 translocation: Association of Rab10-GTP with the exocyst subunit Exoc6/6b.
abstract: Insulin increases glucose transport in fat and muscle cells by stimulating the exocytosis of specialized vesicles containing the glucose transporter GLUT4. This process, which is referred to as GLUT4 translocation, increases the amount of GLUT4 at the cell surface. Previous studies have provided evidence that insulin signaling increases the amount of Rab10-GTP in the GLUT4 vesicles and that GLUT4 translocation requires the exocyst, a complex that functions in the tethering of vesicles to the plasma membrane, leading to exocytosis. In the present study we show that Rab10 in its GTP form binds to Exoc6 and Exoc6b, which are the two highly homologous isotypes of an exocyst subunit, that both isotypes are found in 3T3-L1 adipocytes, and that knockdown of Exoc6, Exoc6b, or both inhibits GLUT4 translocation in 3T3-L1 adipocytes. These results suggest that the association of Rab10-GTP with Exoc6/6b is a molecular link between insulin signaling and the exocytic machinery in GLUT4 translocation.
authors: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Hiroyuki
authors: H
authors: Sano
authors: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors: Grantley R
authors: GR
authors: Peck
authors: Hybrigenics Services SAS, 3-5 Impasse Reille, 75014 Paris, France.
authors: Stephanie
authors: S
authors: Blachon
authors: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. Electronic address: gustav.e.lienhard@dartmouth.edu.
authors: Gustav E
authors: GE
authors: Lienhard
mesh_terms: D016475:3T3 Cells; D000818:Animals; D005089:Exocytosis / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C489222:EXOC6B protein, human; D051275:Glucose Transporter Type 4; D007328:Insulin; D021122:Protein Subunits; C495693:Slc2a4 protein, mouse; D019204:GTP-Binding Proteins; C520736:Rab10 protein, mouse; D020691:rab GTP-Binding Proteins
keywords: Exocyst; GLUT4; Insulin; Rab10