DISTINCT LOCALIZATION OF RENIN AND GLUT-4 IN JUXTAGLOMERULAR CELLS OFMOUSE KIDNEY

The insulin-responsive glucose transporter, GLUT-4, is found primarily in adipocytes and skeletal muscle cells: where it is sequestered in a specialized recycling compartment, from which it can be recruited to the cell surface following insulin stimulation. Lower levels of GLUT-4 are also expressed in other tissues, including the kidney, where it i s present particularly in cells of the afferent arteriole and juxtaglo merular apparatus (JGA). The exact nature of GLUT-4-containing compart ments and their relationship to other regulated trafficking pathways i n different cells are not yet well defined. The trafficking of GLUT-4 has been studied in different cells with regulated secretory pathways, and a recent study shows that, in cardiomyocytes, GLUT-4 is sorted an d packaged into multiple regulated pathways (J. W. Slot, G. Garruti, S . Martin, V. Oorschot, G. Pshuma, E. W. Kraegen, R. Laybutt, G. Thibau lt, and D. E. James. J. Cell Biol. 137: 1243-1254, 1997). In the kidne y, cells of the JGA synthesize and secrete their major product, renin, via a well-established, regulated, secretory pathway. These cells als o express GLUT-4 and thus offer the potential to directly compare the localization and trafficking of GLUT-4 and renin in a unique cell type . The present study was undertaken to investigate the intracellular di stribution of GLUT-4 in mouse kidney cortex and to determine whether G LUT-4 and renin are trafficked in the same or in separate regulated pa thways. Ultrathin cryosections of mouse kidney were labeled by the imm unogold technique and viewed by electron microscopy, demonstrating the distribution of GLUT-4 in cells of the JGA, afferent arteriole, and d istal tubule. In granular cells of the JGA, renin was localized in sec retory granules of the regulated secretory pathway, whereas GLUT-4 lab eling in the same cells was found in a distinct tubulovesicular compar tment located adjacent to the trans-Golgi network. We show that granul ar cells have separate, morphologically distinct compartments for the sequestration of renin and GLUT-4, providing evidence that there may b e distinct pathways for the sorting and trafficking of these two prote ins.