SORTILIN IS A MAJOR PROTEIN-COMPONENT OF GLUT4-CONTAINING VESICLES

In fat and skeletal muscle cells, glucose transporter isoform 4 (Glut4 ) is translocated to the cell surface in response to insulin via a sys tem of specialized recycling vesicles, Besides Glut4, these vesicles i nclude the novel insulin-regulatable aminopeptidase, receptors for ins ulin-like growth factor-II/Man-6-phosphate and transferrin, and a glyc oprotein with the molecular mass of 110 kDa. We report here by the cri teria of the partial protein sequencing and subsequent cDNA cloning th at glycoprotein 110, the last unidentified major protein component of Glut4-containing vesicles, is sortilin, a novel type I receptor-like p rotein recently cloned from human brain (Petersen, C, M,, Nielsen, M. S., Nykjar, A., Jacobsen, L,, Tommerup, N,, Rasmussen, H, H,, Roigaard , H,, Gliemann, J,, Madsen, P,, and Moestrup, S. K, (1997) J, Biol, Ch en, 272, 3599-3605), This protein is highly expressed in fat, brain, a nd lung and is dramatically up-regulated during differentiation of adi pocytes in vitro.