Chloride/bicarbonate exchanger SLC26A7 is localized in endosomes in medullary collecting duct cells and is targeted to the basolateral membrane in hypertonicity and potassium depletion.
SLC26A7 is a Cl(-)/HCO(3)(-) exchanger that is expressed on the basolateral membrane and in the cytoplasm of two distinct acid-secreting epithelial cells: The A-intercalated cells in the kidney outer medullary collecting duct and the gastric parietal cells. The intracellular localization of SLC26A7 suggests the possibility of trafficking between cell membrane and intracellular compartments. For testing this hypothesis, full-length human SLC26A7 cDNA was fused with green fluorescence protein and transiently expressed in MDCK epithelial cells. In monolayer cells in isotonic medium, SLC26A7 showed punctate distribution throughout the cytoplasm. However, in medium that was made hypertonic for 16 h, SLC26A7 was detected predominantly in the plasma membrane. The presence of mitogen-activated protein kinase inhibitors blocked the trafficking of SLC26A7 to the plasma membrane. Double-labeling studies demonstrated the localization of SLC26A7 to the transferrin receptor-positive endosomes. A chimera that was composed of the amino terminal fragment of SLC26A7 and the carboxyl terminal fragment of SLC26A1, and a C-terminal-truncated SLC26A7 were retained in the cytoplasm in hypertonicity. In separate studies, SLC26A7 showed predominant localization in plasma membrane in potassium-depleted isotonic medium (0.5 or 2 mEq/L KCl) versus cytoplasmic distribution in normal potassium isotonic medium (4 mEq/L). It is concluded that SLC26A7 is present in endosomes, and its targeting to the basolateral membrane is increased in hypertonicity and potassium depletion. The trafficking to the cell surface suggests novel functional upregulation of SLC26A7 in states that are associated with hypokalemia or increased medullary tonicity. Additional studies are needed to ascertain the role of SLC26A7 in enhanced bicarbonate absorption in outer medullary collecting duct in hypokalemia and in acid-base regulation in conditions that are associated with increased medullary tonicity.
Xu
Jie
J
Division of Nephrology and Hypertension, Department of Medicine, University of Cincinnati, 231 Albert Sabin Way, MSB 259G, Cincinnati, OH 45267-0585, USA.
Worrell
Roger T
RT
Li
Hong C
HC
Barone
Sharon L
SL
Petrovic
Snezana
S
Amlal
Hassane
H
Soleimani
Manoocher
M
D000818:Animals; D017920:Antiporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006982:Hypertonic Solutions; D007008:Hypokalemia / Q000378:metabolism; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000076988:Sulfate Transporters
D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D006982:Hypertonic Solutions; D011993:Recombinant Fusion Proteins; C455626:SLC26A7 protein, human; C486743:Slc26a7 protein, mouse; C486744:Slc26a7 protein, rat; D000076988:Sulfate Transporters; D049452:Green Fluorescent Proteins; D004247:DNA; D011188:Potassium