Stimulation of renal Na+ dicarboxylate cotransporter 1 by Na+/H+ exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B.
Renal tubular citrate transport is accomplished by electrogenic Na(+) coupled dicarboxylate transporter NaDC-1, a carrier subjected to regulation by acidosis. Trafficking of the Na(+)/H(+) exchanger NHE3 is controlled by NHE regulating factors NHERF-1 and NHERF-2 and the serum and glucocorticoid inducible kinase SGK1. To test for a possible involvement in NaDC-1 regulation, mRNA encoding NaDC-1 was injected into Xenopus oocytes with or without cRNA encoding NHERF-1, NHERF-2, SGK1, SGK2, SGK3, and/or the constitutively active form of the related protein kinase B ((T308,S473D)PKB). Succinate induced inward currents (I(succ)) were taken as a measure of transport rate. Coexpression of neither NHERF-1 nor NHERF-2 in NaDC-1 expressing oocytes significantly altered I(succ). On the other hand, coexpression of SGK1, SGK3, and (T308,S473D)PKB stimulated I(succ), an effect further stimulated by additional coexpression of NHERF-2 but not of NHERF-1. The action of the kinases and NHERF-2 may link urinary citrate excretion to proximal tubular H(+) secretion.
Boehmer
Christoph
C
Department of Physiology I, University of Tübingen, Tübingen D-72076, Germany.
Embark
Hamdy M
HM
Bauer
Anna
A
Palmada
Monica
M
Yun
Chris H
CH
Weinman
Edward J
EJ
Endou
Hitoshi
H
Cohen
Philip
P
Lahme
Sven
S
Bichler
Karl-Horst
KH
Lang
Florian
F
D000818:Animals; D019343:Citric Acid / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D029382:Dicarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D007700:Kinetics; D009687:Nuclear Proteins; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D019802:Succinic Acid / Q000494:pharmacology; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D019343:Citric Acid; D003598:Cytoskeletal Proteins; D029382:Dicarboxylic Acid Transporters; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D017923:Sodium-Hydrogen Exchangers; D019802:Succinic Acid; D027981:Symporters; D000099184:Serum-Glucocorticoid Regulated Kinases; C092524:SLC13A2 protein, human; C490478:Slc13a2 protein, rat; C498832:Slc9a3r2 protein, rat; C093376:sodium-hydrogen exchanger regulatory factor