Alternative splicing and diversity of renal transporters.

The growing molecular identification of renal transporter genes is revealing that alternative splicing is common among transporters. In this paper, I review the physiological consequences of alternative splicing in some genes encoding renal transporters in which spliced isoforms have recently been identified. In some cases, the spliced isoforms resulted in nonfunctional proteins, which, however, possess a dominant negative effect on the cotransporter function, suggesting that the presence of such isoforms can be important in the functional regulation of the transporter. In most transporter genes, however, the spliced isoforms have been shown to be functional, resulting in a variety of physiological consequences, including, for example, changes in the polarization of isoforms to the apical or basolateral membrane, changes in pharmacological or kinetic properties, and changes in tissue distribution or intrarenal localization. In some cases, although the spliced isoform is functional, the consequence of splicing is still unknown. Different regulation among isoforms is an interesting possibility. Thus the diversity of several renal transporters is enhanced by alternative splicing mechanisms.