Cotransporters, WNKs and hypertension: An update

Current Opinion in Nephrology and Hypertension

Volumn 17, Issue 2, 2008, Pages 186-192

  Flatman, Peter W ^a,b  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Diuretics; Hypertension; Protein serine threonine kinases; Sodium chloride symporters; Sodium potassium chloride symporters

Indexed keywords

PROTEIN KINASE WNK1; PROTEIN KINASE WNK4; PROTEIN SERINE THREONINE KINASE; SODIUM CHLORIDE COTRANSPORTER; SODIUM POTASSIUM CHLORIDE COTRANSPORTER;

BARTTER SYNDROME; CELL COMPOSITION; GENE MUTATION; GENETIC VARIABILITY; HYPERCALCIURIA; HYPERKALEMIA; HYPERPLASIA; HYPERTENSION; KIDNEY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ALTERNATIVE SPLICING; ANIMALS; BARTTER SYNDROME; BLOOD PRESSURE; GITELMAN SYNDROME; HUMANS; HYPERTENSION; MICE; MICE, TRANSGENIC; MODELS, ANIMAL; OOCYTES; PROTEIN ISOFORMS; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; SODIUM-POTASSIUM-CHLORIDE SYMPORTERS; SYMPORTERS; XENOPUS;

EID: 39149129333     PISSN: 10624821     EISSN: None     Source Type: Journal    
DOI: 10.1097/MNH.0b013e3282f5244e     Document Type: Review

References (52)

1. Mullins LJ, Bailey MA, Mullins JJ. Hypertension, kidney, and transgenics: a fresh perspective. Physiol Rev 2006; 86:709-746.
2. Rosskopf D, Schürks M, Rimmbach C, Schäfers R. Genetics of arterial hypertension and hypotension. Naunyn Schmiedebergs Arch Pharmacol 2007; 374:429-469.
3. Delpire E, Gagnon KB. SPAK and OSR1, key kinases involved in the regulation of chloride transport. Acta Physiol 2006; 187:103-113.
4. Giménez I. Molecular mechanisms and regulation of furosemide-sensitive Na-K-Cl cotransporters. Curr Opin Nephrol Hypertens 2006; 15:517-523.
5. - flux by altering the phosphorylation state of the Na-K-Cl and K-Cl cotransporters. Physiology 2006; 21:326-335.
6. Flatman PW. Cotransporters, WNKs and hypertension: important leads from the study of monogenetic disorders of blood pressure regulation. Clin Sci 2007; 112:203-216.
7. Gamba G. Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev 2005; 85:423-493.
8. - cotransporter (NKCC2s) splice variants. J Gen Physiol 2005; 126:325-337.
9. - cotransporters. J Biol Chem 2007; 282:18083-18093.
10. - cotransporter NKCC1 are required for its homodimerization. Biochemistry 2007; 46:9630-9637.
11. Jeck N, Waldegger S, Lampert A, et al. Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing to hypertension. Hypertension 2004; 43:1175-1181.
12. Jeck N, Waldegger S, Wissinger B, et al. ClC-Kb mutation revisited: response. Hypertension 2006; 47:E12-E13.
13. - co-transporter. J Am Soc Nephrol 2006; 17:2136-2142.
14. Bailey MA, Cantone A, Yan Q, et al. Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet. Kidney Int 2006; 70:51-59.
15. Oppermann M, Mizel D, Huang G, et al. Macula densa control of renin secretion and preglomerular resistance in mice with selective deletion of the B isoform of the Na,K,2Cl co-transporter. J Am Soc Nephrol 2006; 17:2143-2152.
16. Oppermann M, Mizel D, Kim SM, et al. Renal function in mice with targeted disruption of the A isoform of the Na-K-2Cl co-transporter. J Am Soc Nephrol 2007; 18:440-448. This group explores the functional significance of the different NKCC2 isoforms by selectively knocking out each splice variant in mice. The consequences are not as might be expected from original mRNA distribution and expression data.
17. Starremans PGJF, Kersten FFJ, van den Heuvel LPWJ, et al. Dimeric architecture of the human bumetanide-sensitive Na-K-Cl Co-transporter. J Am Soc Nephrol 2003; 14:3039-3046.
18. Giménez I, Forbush B. Short-term stimulation of the renal Na-K-Cl cotransporter (NKCC2) by vasopressin involves phosphorylation and membrane translocation of the protein. J Biol Chem 2003; 278:26946-26951.
19. 2 terminus of the renal Na-K-Cl cotransporter (NKCC2). Am J Physiol Renal Physiol 2005; 289:F1341-F1345.
20. Moriguchi T, Urushiyama S, Hisamoto N, et al. WNK1 Regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J Biol Chem 2005; 280:42685-42693.
21. - co-transporter NKCC2 by AMP-activated protein kinase (AMPK). Biochem J 2007; 405:85-93. Recent work has focused on the activation of NKCCs by phosphorylation of five conserved threonines in the N-terminus. This paper shows AMPK can bind to the N-terminus of NKCC2 and phosphorylate it on serine influencing transport at rest. Strong support for the idea that CCCs are regulated by several kinases.
22. Ortiz PA. cAMP increases surface expression of NKCC2 in rat thick ascending limbs: role of VAMP. Am J Physiol Renal Physiol 2006; 290:F608-F616. Good discussion of how cAMP (and thus vasopressin) may activate NKCC2 in the TAL by increasing surface expression of the transporter stored below the surface in vesicles.
23. Sonalker PA, Jackson EK. Norepinephrine, via b-adrenoceptors, regulates bumetanide-sensitive cotransporter type 1 expression in thick ascending limb cells. Hypertension 2007; 49:1351-1357.
24. Hong NJ, Garvin JL. Flow increases superoxide production by NADPH oxidase via activation of Na-K-2Cl cotransport and mechanical stress in thick ascending limbs. Am J Physiol Renal Physiol 2007; 292:F993-F998.
25. Riveira-Munoz E, Chang Q, Godefroid N, et al. Transcriptional and functional analyses of SLC12A3 mutations: New clues for the pathogenesis of Gitelman syndrome. J Am Soc Nephrol 2007; 18:1271-1283. Comprehensive discussion of how different types of mutation to SLC12A3 determine the severity of Gitelman's disease.
26. - cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion. J Biol Chem 2006; 281:28755-28763. Establishes for the first time that phosphorylation of two threonine residues in the N-terminus of NCC activates the transporter. These residues and those around them are well conserved throughout the sodium branch of the CCC family and define a regulatory motif in these transporters.
27. Moreno E, Cristóbal PS, Rivera M, et al. Affinity-defining domains in the Na-Cl cotransporter. J Biol Chem 2006; 281:17266-17275.
28. - cotransporter to apical membrane. Am J Physiol Renal Physiol 2007; 293:F662-F669.
29. Orlov SN, Adragna NC, Adarichev VA, Hamet P. Genetic and biochemical determinants of abnormal monovalent ion transport in primary hypertension. Am J Physiol 1999; 276:C511-C536.
30. Garg P, Martin CF, Elms SC, et al. Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol 2007; 292:H2100-H2105.
31. - cotransporter on myogenic and angiotensin II responses of the rat afferent arteriole. Am J Physiol Renal Physiol 2007; 292:F999-F1006.
32. Wall SM, Knepper MA, Hassell KA, et al. Hypotension in NKCC1 null mice: role of the kidneys. Am J Physiol Renal Physiol 2006; 290:F409-F416.
33. - cotransporter (NKCC1/BSC2) to renin secretion. Am J Physiol Renal Physiol 2005; 289:F1185-F1192.
34. Reynolds A, Parris A, Evans LA, et al. Dynamic and differential regulation of NKCC1 by calcium and cAMP in the native human colonic epithelium. J Physiol 2007; 582:507-524.
35. Gagnon KBE, England R, Delpire E. A single binding motif is required for SPAK activation of the Na-K-2Cl cotransporter. Cell Physiol Biochem 2007; 20:131-142. Good discussion of NKCC1's interactions with WNK-SPAK/OSR1. The role of each of the five threonines in the NKCC1 regulatory domain is explored using transport and phosphorylation studies.
36. Gagnon KBE, England R, Diehl L, Delpire E. Apoptosis-associated tyrosine kinase scaffolding of protein phosphatase 1 and SPAK reveals a novel pathway for Na-K-2C1 cotransporter regulation. Am J Physiol Cell Physiol 2007; 292:C1809-C1815. A yeast two-hybrid screen identifies another possible SPAK/OSR1 binding partner, AATYK. This brings a phosphatase into proximity with SPAK/OSR1 to facilitate their dephosphorylation and inactivation.
37. Wilson FH, Disse-Nicodème S, Choate KA, et al. Human hypertension caused by mutations in WNK kinases. Science 2001; 293:1107-1112.
38. Xu BE, English JM, Wilsbacher JL, et al. WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem 2000; 275:16795-16801.
39. Subramanya AR, Yang CL, McCormick JA, Ellison DH. WNK kinases regulate sodium chloride and potassium transport by the aldosterone-sensitive distal nephron. Kidney Int 2006; 70:630-634.
40. + homeostasis. Proc Natl Acad Sci USA 2007; 104:4025-4029. Clear discussion of how the kidney may respond differently (and appropriately) to aldosterone depending on whether it was released in response to volume contraction or hyperkalaemia.
41. Golbang AP, Cope G, Hamad A, et al. Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved. Am J Physiol Renal Physiol 2006; 291:F1369-F1376.
42. Cope G, Murthy M, Golbang AP, et al. WNK1 affects surface expression of the ROMK potassium channel independent of WNK4. J Am Soc Nephrol 2006; 17:1867-1874.
43. - cotransporters. Am J Physiol Renal Physiol 2007; 292:F1197-F1207.
44. + channel in vitro and in vivo. Proc Natl Acad Sci USA 2007; 104:4020-4024.
45. Yang SS, Yamauchi K, Rai T, et al. Regulation of apical localization of the thiazide-sensitive NaCl cotransporter by WNK4 in polarized epithelial cells. Biochem Biophys Res Commun 2005; 330:410-414.
46. D561A/+ knockin mouse model. Cell Metab 2007; 5:331-344. Comprehensive study using gene knockin to determine effects of mutant (PHAII) WNK4. Discusses advantages of this approach. Establishes operation of WNK → SPAK/OSR1 →NCC pathway in vivo.
47. Lalioti MD, Zhang J, Volkman HM, et al. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet 2006; 38:1124-1132. Comprehensive study using transgenic mice to determine effects of mutant (PHAII) WNK4. Gives a clear account of the broad range of technologies needed to address the issue.
48. - permeability. FEBS Lett 2007; 581:3887-3891.
49. O'Reilly M, Marshall E, MacGillivray T, et al. Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo. J Am Soc Nephrol 2006; 17:2402-2413.
50. Zagórska A, Pozo-Guisado E, Boudeau J, et al. Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress. J Cell Biol 2007; 176:89-100. Rigorous biochemical analysis of the activation of WNK1 and SPAK/OSR1 in cells following hyperosmotic challenge. Binding of WNK1 to SPAK/OSR1 analysed and distribution of WNK1 in cell followed using GFP tag.
51. Delpire E, Gagnon KBE. Genome-wide analysis of SPAK/OSR1 binding motifs. Physiol Genomics 2007; 28:223-231.
52. Villa F, Goebel J, Rafiqi FH, et al. Structural insights into the recognition of substrates and activators by the OSR1 kinase. EMBO Rep 2007; 8:839-845. Describes crystallization of C-terminal of OSR1 and subsequent determination of structure. This led to the discovery of a new protein fold (SPOC) unique to SPAK/OSR1 and which is involved in their interactions with WNKs and CCCs. Could become an important drug target.