Altered GLUT4 trafficking in adipocytes in the absence of the GTPase Arfrp1 |
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Authors: | Deike Hesse Angela Hommel Alexander Jaschke Ulrike Bernhardt Reinhart Kluge Achim D Gruber Hans-Georg Joost |
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Institution: | a Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany b Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany c Department of Veterinary Pathology, Freie Universität Berlin, D-14163 Berlin, Germany |
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Abstract: | The GTPase ADP-ribosylation factor related protein 1 (ARFRP1) controls the recruitment of proteins such as golgin-245 to the trans-Golgi. ARFRP1 is highly expressed in adipose tissues in which the insulin-sensitive glucose transporter GLUT4 is processed through the Golgi to a specialized endosomal compartment, the insulin-responsive storage compartment from which it is translocated to the plasma membrane in response to a stimulation of cells by insulin. In order to examine the role of ARFRP1 for GLUT4 targeting, subcellular distribution of GLUT4 was investigated in adipose tissue specific Arfrp1 knockout (Arfrp1ad−/−) mice. Immunohistochemical and ultrastructural studies of brown adipocytes demonstrated an abnormal trans-Golgi in Arfrp1ad−/− adipocytes. In addition, in Arfrp1ad−/− adipocytes GLUT4 protein accumulated at the plasma membrane rather than being sequestered in an intracellular compartment. A similar missorting of GLUT4 was produced by siRNA-mediated knockdown of Arfrp1 in 3T3-L1 adipocytes which was associated with significantly elevated uptake of deoxyglucose under basal conditions. Thus, Arfrp1 appears to be involved in sorting of GLUT4. |
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Keywords: | ARF-proteins Glucose transporter GLUT4 Golgi apparatus Golgin proteins |
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