Molecular characterization of the murine Slc26a6 anion exchanger: functional comparison with Slc26a1.
We report the molecular and functional characterization of murine Slc26a6, the putative apical chloride-formate exchanger of the proximal tubule. The Slc26a6 transcript is expressed in several tissues, including kidney. Alternative splicing of the second exon generates two distinct isoforms, denoted Slc26a6a and Slc26a6b, which differ in the inclusion of a 23-residue NH(2)-terminal extension. Functional comparison with murine Slc26a1, the basolateral oxalate exchanger of the proximal tubule, reveals a number of intriguing differences. Whereas Slc26a6 is capable of Cl(-), SO, formate, and oxalate uptake when expressed in Xenopus laevis oocytes, Slc26a1 transports only SO and oxalate. Measurement of intracellular pH during the removal of extracellular Cl(-) in the presence and absence of HCO indicates that Slc26a6 functions as both a Cl(-)/HCO and a Cl(-)/OH(-) exchanger; simultaneous membrane hyperpolarization during these experimental maneuvers reveals that HCO and OH(-) transport mediated by Slc26a6 is electrogenic. Cis-inhibition and efflux experiments indicate that Slc26a6 can mediate the exchange of both Cl(-) and SOwith a number of substrates, including formate and oxalate. In contrast, SO and oxalate transport by Slc26a1 are mutually cis-inhibited but activated significantly by extracellular halides, lactate, and formate. The data indicate that Slc26a6 encodes an apical Cl(-)/formate/oxalate and Cl(-)/base exchanger and reveal significant mechanistic differences between apical and basolateral oxalate exchangers of the proximal tubule.
Xie
Qizhi
Q
Division of Nephrology, Nashville Veterans Affairs Medical Center, Tennessee 37232, USA.
Welch
Rick
R
Mercado
Adriana
A
Romero
Michael F
MF
Mount
David B
DB
D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D002712:Chlorides / Q000378:metabolism; D002875:Chromosomes / Q000737:chemistry / Q000235:genetics; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D000076988:Sulfate Transporters; D013431:Sulfates / Q000378:metabolism; D014982:Xenopus laevis
D027321:Anion Transport Proteins; D017920:Antiporters; D002712:Chlorides; C466903:Slc26a1 protein, mouse; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; D013431:Sulfates