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.
Hesse
Deike
D
Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany.
Hommel
Angela
A
Jaschke
Alexander
A
Moser
Markus
M
Bernhardt
Ulrike
U
Zahn
Claudia
C
Kluge
Reinhart
R
Wittschen
Petra
P
Gruber
Achim D
AD
Al-Hasani
Hadi
H
Joost
Hans-Georg
HG
Schürmann
Annette
A
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