Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure

Human Molecular Genetics

Volumn 18, Issue 20, 2009, Pages 3978-3986

  Ohta, Akihito ^a   Rai, Tatemitsu ^a   Yui, Naofumi ^a   Chiga, Motoko ^a   Yang, Sung Sen ^b   Lin, Shih Hua ^b   Sohara, Eisei ^a   Sasaki, Sei ^a   Uchida, Shinichi ^a  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b TRI SERVICE GENERAL HOSPITAL   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

KINASE OSR1; KINASE SPAK; POTASSIUM CHANNEL; PROTEIN KINASE; PROTEIN KINASE WNK4; PROTEIN MAXI K; PROTEIN ROMK; SODIUM CHANNEL; SODIUM CHLORIDE COTRANSPORTER; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BLOOD PRESSURE MEASUREMENT; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; FEMALE; GENE DELETION; GENE FUNCTION; GENE MUTATION; GENE TARGETING; HUMAN; HUMAN CELL; HYPOKALEMIA; KNOCKOUT MOUSE; MALE; METABOLIC ALKALOSIS; MOUSE; NONHUMAN; PHOSPHORYLATION; POTASSIUM EXCRETION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PSEUDOHYPOALDOSTERONISM; REGULATORY MECHANISM; SODIUM EXCRETION; SODIUM RESTRICTION; WILD TYPE;

AMINO ACID SEQUENCE; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD PRESSURE; DISEASE MODELS, ANIMAL; FEMALE; GENE SILENCING; MALE; MICE; MICE, INBRED C57BL; MOLECULAR SEQUENCE DATA; PHOSPHORYLATION; POTASSIUM; PROTEIN-SERINE-THREONINE KINASES; PSEUDOHYPOALDOSTERONISM; RECEPTORS, DRUG; SODIUM; SYMPORTERS;

MUS;

EID: 70349581037     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddp344     Document Type: Article

References (27)

1. Gordon, R.D. (1986) Syndrome of hypertension and hyperkalemia with normal glomerular filtration rate. Hypertension, 8, 93-102.
2. Schambelan, M., Sebastian, A. and Rector, F.C. Jr (1981) Mineralocorticoid-resistant renal hyperkalemia without salt wasting (type II pseudohypoaldosteronism): Role of increased renal chloride reabsorption. Kidney Int., 19, 716-727.
3. Achard, J.M., Disse-Nicodeme, S., Fiquet-Kempf, B. and Jeunemaitre, X. (2001) Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome). Clin. Exp. Pharmacol. Physiol., 28, 1048-1052.
4. Wilson, F.H., Disse-Nicodeme, S., Choate, K.A., Ishikawa, K., Nelson-Williams, C., Desitter, I., Gunel, M., Milford, D.V., Lipkin, G.W., Achard, J.M. et al. (2001) Human hypertension caused by mutations in WNK kinases. Science, 293, 1107-1112.
5. Mayan, H., Vered, I., Mouallem, M., Tzadok-Witkon, M., Pauzner, R. and Farfel, Z. (2002) Pseudohypoaldosteronism type II: Marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. J. Clin. Endocrinol. Metab., 87, 3248-3254.
6. Yang, C.L., Angell, J., Mitchell, R. and Ellison, D.H. (2003) WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J. Clin. Invest., 111, 1039-1045.
7. Wilson, F.H., Kahle, K.T., Sabath, E., Lalioti, M.D., Rapson, A.K., Hoover, R.S., Hebert, S.C., Gamba, G. and Lifton, R.P. (2003) Molecular pathogenesis of inherited hypertension with hyperkalemia: The Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc. Natl. Acad. Sci. U.S.A., 100, 680-684.
8. Kahle, K.T., Gimenez, I., Hassan, H., Wilson, F.H., Wong, R.D., Forbush, B., Aronson, P.S. and Lifton, R.P. (2004) WNK4 regulates apical and basolateral Cl- flux in extrarenal epithelia. Proc. Natl. Acad. Sci. U.S.A., 101, 2064-2069.
9. Ring, A.M., Cheng, S.X., Leng, Q., Kahle, K.T., Rinehart, J., Lalioti, M.D., Volkman, H.M., Wilson, F.H., Hebert, S.C. and Lifton, R.P. (2007) WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A., 104, 4020-4024.
10. Kahle, K.T., Wilson, F.H., Leng, Q., Lalioti, M.D., O'Connell, A.D., Dong, K., Rapson, A.K., MacGregor, G.G., Giebisch, G., Hebert, S.C. et al. (2003) WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Nat. Genet., 35, 372-376.
11. Yang, S.S., Yamauchi, K., Rai, T., Hiyama, A., Sohara, E., Suzuki, T., Itoh, T., Suda, S., Sasaki, S. and Uchida, S. (2005) Regulation of apical localization of the thiazide-sensitive NaCl cotransporter by WNK4 in polarized epithelial cells. Biochem. Biophys. Res. Commun., 330, 410-414.
12. Richardson, C. and Alessi, D.R. (2008) The regulation of salt transport and blood pressure by the WNK-SPAK/OSR1 signalling pathway. J. Cell. Sci., 121, 3293-3304.
13. Richardson, C., Rafiqi, F.H., Karlsson, H.K., Moleleki, N., Vandewalle, A., Campbell, D.G., Morrice, N.A. and Alessi, D.R. (2008) Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J. Cell. Sci., 121, 675-684.
14. Lalioti, M.D., Zhang, J., Volkman, H.M., Kahle, K.T., Hoffmann, K.E., Toka, H.R., Nelson-Williams, C., Ellison, D.H., Flavell, R., Booth, C.J. et al. (2006) Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat. Genet., 38, 1124-1132.
15. Yang, S.S., Morimoto, T., Rai, T., Chiga, M., Sohara, E., Ohno, M., Uchida, K., Lin, S.H., Moriguchi, T., Shibuya, H. et al. (2007) Molecular pathogenesis of pseudohypoaldosteronism type II: Generation and analysis of a Wnk4(D561A/+) knockin mouse model. Cell Metab., 5, 331-344.
16. Schultheis, P.J., Lorenz, J.N., Meneton, P., Nieman, M.L., Riddle, T.M., Flagella, M., Duffy, J.J., Doetschman, T., Miller, M.L. and Shull, G.E. (1998) Phenotype resembling Gitelman's syndrome in mice lacking the apical Na+-Cl- cotransporter of the distal convoluted tubule. J. Biol. Chem., 273, 29150-29155.
17. Moriguchi, T., Urushiyama, S., Hisamoto, N., Iemura, S., Uchida, S., Natsume, T., Matsumoto, K. and Shibuya, H. (2005) WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J. Biol. Chem., 280, 42685-42693.
18. Pacheco-Alvarez, D., Cristobal, P.S., Meade, P., Moreno, E., Vazquez, N., Munoz, E., Diaz, A., Juarez, M.E., Gimenez, I. and Gamba, G. (2006) The Na+:CL- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion. J. Biol. Chem., 281, 28755-28763.
19. McCormick, J.A., Yang, C.L. and Ellison, D.H. (2008) WNK kinases and renal sodium transport in health and disease: An integrated view. Hypertension, 51, 588-596.
20. Rinehart, J., Kahle, K.T., de Los Heros, P., Vazquez, N., Meade, P., Wilson, F.H., Hebert, S.C., Gimenez, I., Gamba, G. and Lifton, R.P. (2005) WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc. Natl. Acad. Sci. U.S.A., 102, 16777-16782.
21. Yang, C.L., Zhu, X. and Ellison, D.H. (2007) The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J. Clin. Invest., 117, 3403-3411.
22. Zambrowicz, B.P., Abuin, A., Ramirez-Solis, R., Richter, L.J., Piggott, J., BeltrandelRio, H., Buxton, E.C., Edwards, J., Finch, R.A., Friddle, C.J. et al. (2003) Wnk1 kinase deficiency lowers blood pressure in mice: A gene-trap screen to identify potential targets for therapeutic intervention. Proc. Natl. Acad. Sci. U.S.A., 100, 14109-14114.
23. Sohara, E., Rai, T., Yang, S.S., Uchida, K., Nitta, K., Horita, S., Ohno, M., Harada, A., Sasaki, S. and Uchida, S. (2006) Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation. Proc. Natl. Acad. Sci. U.S.A., 103, 14217-14222.
24. Sakai, K. and Miyazaki, J. (1997) A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission. Biochem. Biophys. Res. Commun., 237, 318-324.
25. Mills, P.A., Huetteman, D.A., Brockway, B.P., Zwiers, L.M., Gelsema, A.J., Schwartz, R.S. and Kramer, K. (2000) A new method for measurement of blood pressure, heart rate, and activity in the mouse by radiotelemetry. J. Appl. Physiol., 88, 1537-1544.
26. Whitesall, S.E., Hoff, J.B., Vollmer, A.P. and D'Alecy, L.G. (2004) Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods. Am. J. Physiol. Heart Circ. Physiol., 286, H2408-H2415.
27. Gagnon, K.B., England, R. and Delpire, E. (2006) Characterization of SPAK and OSR1, regulatory kinases of the Na-K-2Cl cotransporter. Mol. Cell. Biol., 26, 689-698.