Altered GLUT4 trafficking in adipocytes in the absence of the GTPase Arfrp1

作者：Hesse Deike; Hommel Angela; Jaschke Alexander; Moser Markus; Bernhardt Ulrike; Zahn Claudia; Kluge Reinhart; Wittschen Petra; Gruber Achim D; Al Hasani Hadi; Joost Hans Georg; Schurmann Annette^*

来源：Biochemical and Biophysical Research Communications, 2010, 394(4): 896-903.

DOI：10.1016/j.bbrc.2010.03.059

• ARF-proteins
• Glucose transporter GLUT4
• Golgi apparatus
• Golgin proteins

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.

• 出版日期2010-4-16