A Leu-Leu sequence is essential for COOH-terminal targeting signal of GLUT4 glucose transporter in fibroblasts.

In the insulin-responsive tissues, muscle and adipose, the GLUT4 glucose transporter isoform accounts for most of the increase in hexose flux in response to hormone. In these cell types, as well as in fibroblasts transfected with cDNAs encoding the transporters, GLUT1 and GLUT4 are sorted to different subcellular locations. In the latter, GLUT1 is found primarily at the cell surface whereas GLUT4 localizes to the interior of the cell in a perinuclear distribution. The construction and analysis of chimeras of these two transporter isoforms have allowed identification of the COOH-terminal 30 amino acids as a critical sorting signal for differential localization of the transporters. In this study, we show that 2 residues present in the GLUT4 COOH terminus, Leu-489 and Leu-490, are critical for the intracellular sequestration of this isoform in NIH3T3 cells.