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 ((PKB)-P-T308,S473D). Succinate induced inward currents (I-succ) were taken as a measure of transport rate. Coexpression of neither NHERF-I nor NHERF-2 in NaDC-1 expressing oocytes significantly altered I-succ. On the other hand, coexpression of SGK1, SGK3, and (PKB)-P-T308,S473D 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. (C) 2003 Elsevier Inc. All rights reserved.