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Publication : Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes.

First Author  Shi J Year  2005
Journal  Dev Cell Volume  9
Issue  1 Pages  99-108
PubMed ID  15992544 Mgi Jnum  J:99400
Mgi Id  MGI:3582104 Doi  10.1016/j.devcel.2005.04.004
Citation  Shi J, et al. (2005) Sortilin Is Essential and Sufficient for the Formation of Glut4 Storage Vesicles in 3T3-L1 Adipocytes. Dev Cell 9(1):99-108
abstractText  Impaired translocation of the glucose transporter isoform 4 (Glut4) to the plasma membrane in fat and skeletal muscle cells may represent a primary defect in the development of type 2 diabetes mellitus. Glut4 is localized in specialized storage vesicles (GSVs), the biological nature and biogenesis of which are not known. Here, we report that GSVs are formed in differentiating 3T3-L1 adipocytes upon induction of sortilin on day 2 of differentiation. Forced expression of Glut4 prior to induction of sortilin leads to rapid degradation of the transporter, whereas overexpression of sortilin increases formation of GSVs and stimulates insulin-regulated glucose uptake. Knockdown of sortilin decreases both formation of GSVs and insulin-regulated glucose uptake. Finally, we have reconstituted functional GSVs in undifferentiated cells by double transfection of Glut4 and sortilin. Thus, sortilin is not only essential, but also sufficient for biogenesis of GSVs and acquisition of insulin responsiveness in adipose cells.
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