Altered GLUT4 trafficking in adipocytes in the absence of the GTPase Arfrp1.
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 (Arfrp1(ad)(-/-)) mice. Immunohistochemical and ultrastructural studies of brown adipocytes demonstrated an abnormal trans-Golgi in Arfrp1(ad)(-/-) adipocytes. In addition, in Arfrp1(ad)(-/-) 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.
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
Deike
D
Hesse
Angela
A
Hommel
Alexander
A
Jaschke
Markus
M
Moser
Ulrike
U
Bernhardt
Claudia
C
Zahn
Reinhart
R
Kluge
Petra
P
Wittschen
Achim D
AD
Gruber
Hadi
H
Al-Hasani
Hans-Georg
HG
Joost
Annette
A
Schürmann
D041721:3T3-L1 Cells; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D052437:Adipocytes, Brown / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport; D021601:trans-Golgi Network / Q000378:metabolism* / Q000648:ultrastructure
D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse; D020727:ADP-Ribosylation Factors; C531986:Arfrp1 protein, mouse