Stimulation of renal Na + dicarboxylate cotransporter 1 by Na +/H + exchanger regulating factor 2, serum and glucocorticoid inducible kinase isoforms, and protein kinase B

• Published in: Biochemical and biophysical research communications Vol. 313; no. 4; pp. 998 - 1003
• Main Authors: Boehmer, Christoph, Embark, Hamdy M, Bauer, Anna, Palmada, Monica, Yun, Chris H, Weinman, Edward J, Endou, Hitoshi, Cohen, Philip, Lahme, Sven, Bichler, Karl-Horst, Lang, Florian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.01.2004
• Subjects: Alkalosis; Animals; Citrate; Citric Acid - metabolism; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Dicarboxylic Acid Transporters - genetics; Dicarboxylic Acid Transporters - metabolism; Female; Humans; Immediate-Early Proteins; In Vitro Techniques; Insulin; Kidney; Kidney - metabolism; Kidney Tubules, Proximal - metabolism; Kinetics; Na +/H + exchanger; Nuclear Proteins; Oocytes - drug effects; Oocytes - metabolism; Organic Anion Transporters, Sodium-Dependent - genetics; Organic Anion Transporters, Sodium-Dependent - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Proximal tubule; Rats; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Sodium-Hydrogen Exchangers; Succinic Acid - pharmacology; Symporters - genetics; Symporters - metabolism; Urolithiasis; Xenopus laevis; Proximal tubule; Urolithiasis; Citrate; Na +/H + exchanger; Insulin; Kidney; Alkalosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.12.011

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,S473DPKB). 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,S473DPKB 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.