Apical salt absorption by the renal proximal tubule the (PT) is thought to be accomplished by a coordinated action, of Na+-H+ exchange and Cl-formate, Cl-oxalate, or Cl-base exchange. The major entry step for Na + is mediated by NHE3, which exchanges tubular Na + with intracellular H+. It is however unclear which molecule(s) function in the apical absorption of CI. Recent studies have suggested that the anion exchanger Slc26a6 is a crucial anion exchanger in the PT. ? This versatile transporter is capable of exchanging CI with multiple substrates, including formate, oxalate, SO42-, HCO3-, and OH-, at least when expressed in Xenopus oocytes. The sponsoring laboratory has cloned and characterized the human SLC26A6 cDNA, two distinct amino-terminal isoforms of murine Slc26a6, and is actively studying the function and regulation of these exchangers. We propose to further characterize the physiology of Slc26a6 by attempting to determine the complete intra-renal distribution of the two N-terminal isoforms of Slc26a6 using both nucleic acid and antibody probes. We will further address the functional attributes of this transporter and selected non-mammalian SLC26A6 orthologs by characterizing their anion specificity, kinetics, and pharmacology. Finally, we will define the role of specific transmembrane domains of SLC26A6 by generating chimeras and point mutants from Slc26a6 with other functionally divergent paralogs such as Slc26a9, in order to identify and compare the specific molecular determinants of their distinct functional properties. ? ? ?
| Chang, Min-Hwang; Plata, Consuelo; Zandi-Nejad, Kambiz et al. (2009) Slc26a9--anion exchanger, channel and Na+ transporter. J Membr Biol 228:125-40 |
| Nakada, Tsutomu; Zandi-Nejad, Kambiz; Kurita, Yukihiro et al. (2005) Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater. Am J Physiol Regul Integr Comp Physiol 289:R575-R585 |
