New insights into epithelial sodium channel function in the kidney: Site of action, regulation by ubiquitin ligases, serum- and glucocorticoid-inducible kinase and proteolysis

Current Opinion in Nephrology and Hypertension

Volumn 13, Issue 5, 2004, Pages 541-548

  Thomas, Christie P ^a,b   Itani, Omar A ^a  

^a UNIVERSITY OF IOWA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Aldosterone; Channel activating protease; Connecting tubule; ENaC; Furin

Indexed keywords

PROTEIN SUBUNIT; SERUM AND GLUCOCORTICOID REGULATED KINASE 1; SODIUM CHANNEL; UBIQUITIN PROTEIN LIGASE;

CELL MEMBRANE TRANSPORT; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME REGULATION; HUMAN; KIDNEY COLLECTING TUBULE; KIDNEY EPITHELIUM; KIDNEY FUNCTION; KIDNEY TUBULE; MOLECULE; NONHUMAN; PHENOTYPE; POTASSIUM TRANSPORT; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; SODIUM TRANSPORT;

ANIMALS; BLOOD PROTEINS; EPITHELIUM; HUMANS; IMMEDIATE-EARLY PROTEINS; KIDNEY; NUCLEAR PROTEINS; PROTEIN-SERINE-THREONINE KINASES; SODIUM CHANNELS; UBIQUITIN-PROTEIN LIGASES;

EID: 4344592072     PISSN: 10624821     EISSN: None     Source Type: Journal    
DOI: 10.1097/00041552-200409000-00010     Document Type: Review

References (74)

1. de la Rosa DA, Canessa CM, Fyfe GK, et al. Structure and regulation of amiloride-sensitive sodium channels. Annu Rev Physiol 2000; 62:573-594.
2. Kellenberger S, Schild L. Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev 2002; 82:735-767.
3. Garty H, Palmer LG. Epithelial sodium channels: function, structure, and regulation. Physiol Rev 1997; 77:359-396.
4. Shimkets RA, Warnock DG, Bositis CM, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell 1994; 79:407-414.
5. Hansson JH, Nelson-Williams C, Suzuki H, et al. Human hypertension caused by mutation in the gamma subunit of the epithelial sodium channel: Genetic heterogeneity of Liddle's syndrome. Nat Genet 1995; 11:76-82.
6. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell 2001; 104:545-556.
7. Chang SS, Grunder S, Hanukoglu A, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 1996; 12:248-253.
8. Strautnieks SS, Thompson RJ, Gardiner RM, et al. A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three psuedohypoaldosteronism type 1 families. Nat Genet 1996; 13:248-250.
9. Hummler E, Barker P, Talbot C, et al. A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. Proc Natl Acad Sci USA 1997; 94:11710-11715.
10. Barker P, Nguyen M, Gatzy J, et al. Role of gENaC subunit in lung liquid clearance and electrolye balance in newborn mice. J Clin Invest 1998; 102:1634-1640.
11. + channel in mice: Hyperkalemia and neonatal death associated with pseudohypoaldosteronism phenotype. Proc Natl Acad Sci USA 1999; 96:1727-1731.
12. + channel deleted in Liddle's syndrome. EMBO J 1996; 15:2371-2380.
13. + channel. FASEB J 2001; 15:204-214.
14. Malbert-Colas L, Nicolas G, Galand C, et al. Identification of new partners of the epithelial sodium channel alpha subunit. C R Biol 2003; 326:615-624.
15. + channel by interaction of NEDD4 with a PY motif deleted in Liddle's syndrome. J Biol Chem 1998; 273:30012-30017.
16. + channel by Nedd4 in Liddle's syndrome. J Clin Invest 1999; 103:667-673.
17. +-channel subunits. Biochem J 2000; 345:503-509.
18. + channel by human Nedd4. J Biol Chem 2001; 276:28321-28326.
19. Harvey KF, Dinudom A, Cook DI, et al. The nedd4-like protein kiaa0439 is a potential regulator of the epithelial sodium channel. J Biol Chem 2001; 276:8597-8601.
20. + channel (ENaC) by ubiquitination. EMBO J 1997; 16:6325-6336.
21. Hiltunen TP, Hannila-Handelberg T, Petajaniemi N, et al. Liddle's syndrome associated with a point mutation in the extracellular domain of the epithelial sodium channel gamma subunit. J Hypertens 2002; 20:2383-2390.
22. Funder JW. Glucocorticoid and mineralocorticoid receptors: biology and clinical relevance. Ann Rev Med 1997; 48:231-240.
23. Mick VE, Itani OA, Loftus RW, et al. The α subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5′ flanking region of the gene. Mol Endocrinol 2001; 15:575-588.
24. Chen SY, Bhargava A, Mastroberardino L, et al. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci USA 1999; 96:2514-2519.
25. Naray-Fejes-Toth A, Canessa C, Cleaveland ES, et al. sgk is an aldosterone-induced kinase in the renal collecting duct. J Biol Chem 1999; 274:16973-16978.
26. + reabsorption by the aldosterone-induced small G protein K-Ras2A. J Biol Chem 1999; 274:35449-35454.
27. Velazquez H, Bartiss A, Bernstein P, et al. Adrenal steroids stimulate thiazide-sensitive NaCl transport by rat renal distal tubules. Am J Physiol Renal Physiol 1996; 270:F211-F219.
28. Bostanjoglo M, Reeves WB, Reilly RF, et al. 11Beta-hydroxysteroid dehydrogenase, mineralocorticoid receptor, and thiazide-sensitive Na-Cl cotransporter expression by distal tubules. J Am Soc Nephrol 1998; 9:1347-1358.
29. + channel in rabbit kidney. Pflugers Arch 1999; 438:354-360.
30. Loffing J, Pietri L, Aregger F, et al. Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets. Am J Physiol Renal Physiol 2000; 279:F252-F258.
31. +-loaded. Immunostaining of mouse kidney shows αENaC expression in the late distal convoluted tubule and connecting tubule. The authors suggest that ENaC activity in the connecting tubule may compensate for loss of ENaC in the CCD.
32. +-reabsorptive capacity that is 10 times higher than the CCD.
33. Xu JZ, Hall AE, Peterson LN, et al. Localization of the ROMK protein on apical membranes of rat kidney nephron segments. Am J Physiol Renal Physiol 1997; 273:F739-F748.
34. Mennitt PA, Wade JB, Ecelbarger CA, et al. Localization of ROMK channels in the rat kidney. J Am Soc Nephrol 1997; 8:1823-1830.
35. Naray-Fejes-Toth A, Fejes-Toth G. Extranuclear localization of endogenous 11beta-hydroxysteroid dehydrogenase-2 in aldosterone target cells. Endocrinology 1998; 139:2955-2959.
36. Rundle SE, Smith AI, Stockman D, et al. Immunocytochemical demonstration of mineralocorticoid receptors in rat and human kidney. J Steroid Biochem 1989; 33:1235-1242.
37. Loffing J, Zecevic M, Feraille E, et al. Aldosterone induces rapid apical translocation of ENaC in early portion of renal collecting system: possible role of SGK. Am J Physiol Renal Physiol 2001; 280:F675-F682.
38. 2+-dependent plasma membrane localization. J Biol Chem 1997; 272:32329-32336.
39. + channel regulation. Am J Physiol Renal Physiol 2001; 281:F469-F477.
40. +. J Biol Chem 1999; 274:12525-12530.
41. Lott JS, Coddington-Lawson SJ, Teesdale-Spittle PH, et al. A single WW domain is the predominant mediator of the interaction between the human ubiquitin-protein ligase Nedd4 and the human epithelial sodium channel. Biochem J 2002; 361:481-488.
42. + channel. J Biol Chem 2003; 278:20019-20028. The interactions of each WW domain of Nedd4 and Nedd4-2 with the PY domain of ENaC were quantitated and compared directly by intrinsic tryptophan fluorescence. The WW3 domains of both Nedd proteins are equally efficient in binding to ENaC.
43. McDonald FJ, Western AH, McNeil JD, et al. Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol 2002; 283:F431-F436.
44. Itani OA, Campbell JR, Herrero J, et al. Alternate promoters and variable splicing lead to hNedd4-hNedd2 isoforms with a C2 domain and varying number of WW domains. Am J Physiol Renal Physiol 2003; 285:F916-F929.
45. + channel cell surface expression. EMBO J 2001; 20:7052-7059.
46. Snyder PM, Olson DR, Thomas BC. SGK modulates Nedd4-Nedd2-mediated inhibition of ENaC. J Biol Chem 2002; 277:5-8.
47. Snyder PM, Steines JC, Olson DR. Relative contribution of Nedd4 and Nedd4-Nedd2 to ENaC regulation in epithelia determined by RNA interference. J Biol Chem 2004; 279:5042-5046. Studies done with small interfering RNA show that knocking down Nedd4-2 increases ENaC activity in H441 and FRT epithelia while knock-down of Nedd4 has no effect. Authors show that the presence of phosphorylated residues on Nedd4-2 is important for SGK activity, and that the early glucocorticoid effect on ENaC is predominantly through the inactivation of Nedd4-2 by SGK1.
48. de La Rosa DA, Zhang P, Naray-Fejes-Toth A, et al. The serum and glucocorticoid kinase sgk increases the abundance of epithelial sodium channels in the plasma membrane of Xenopus oocytes. J Biol Chem 1999; 274:37834-37839.
49. + channel (ENaC) and CFTR: implications for cystic fibrosis. Cell Physiol Biochem 2001; 11:209-218.
50. + transport. Am J Physiol Cell Physiol 2002; 282:C494-C500.
51. Naray-Fejes-Toth A, Helms MN, Stokes JB, et al. Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase, SGK1: structure/function studies. Mol Cell Endocrinol 2004; 217:197-202.
52. Alvarez de la Rosa D, Coric T, Todorovic N, et al. Distribution and regulation of expression of serum- and glucocorticoid-induced kinase-1 in the rat kidney. J Physiol 2003; 551:455-466.
53. + transport. Am J Physiol Renal Physiol 2002; 283:F377-F387.
54. + homeostasis and hypertension. Endocr Rev 2002; 23:258-275.
55. + transport.
56. Pradervand S, Vandewalle A, Bens M, et al. Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome. J Am Soc Nephrol 2003; 14:2219-2228.
57. +ATPase by the serum and glucocorticoid-dependent kinase sgk1. Pfluegers Arch Eur J Physiol 2002; 444:426-431.
58. + channel ROMK1. J Am Soc Nephrol 2002; 13:2823-2830.
59. Yoo D, Kim BY, Campo C, et al. Cell surface expression of the ROMK (Kir 1.1) channel Is regulated by the aldosterone-induced kinase, sgk-1, and protein kinase A. J Biol Chem 2003; 278:23066-23075.
60. +) retention in the sgk1-knockout mouse. J Clin Invest 2002; 110:1263-1268.
61. Kobayashi T, Deak M, Morrice N, et al. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J 1999; 344:189-197.
62. + transport in Xenopus oocytes expressing all three ENaC subunits, similar to the effect of SGK1.
63. + channel involves proteolytic processing of the {alpha}- and {gamma}-subunits. J Biol Chem 2003; 278:37073-37082. Expression of tagged-ENaC subunits in MDCK and CHO cells results in glycosylation of all three subunits and proteolytic cleavage of α and γENaC. Cleavage is associated with the formation of complex N-glycans; moreover, all cleaved fragments remain associated with the channel.
64. Hughey RP, Bruns JB, Kinlough CL, et al. Epithelial sodium channels are activated by furin-dependent proteolysis. J Biol Chem 2004; 279:18111-18114. Epithelial sodium channels are activated by furin-dependent proteolysis: the authors identify consensus furin cleavage sites on α and γENaC. Mutations in these sites lead to a reversible reduction in ENaC activity in two heterologous expression systems. Inactivating furin leads to lower endogenous ENaC activity in mpkCCD epithelia.
65. Rockwell NC, Krysan DJ, Komiyama T, et al. Precursor processing by kex2/ furin proteases. Chem Rev 2002; 102:4525-4548.
66. Vallet V, Chraibi A, Gaeggeler HP, et al. An epithelial serine protease activates the amiloride-sensitive sodium channel. Nature 1997; 389:607-610.
67. Vuagniaux G, Vallet V, Jaeger NF, et al. Activation of the amiloride-sensitive epithelial sodium channel by the serine protease mCAP1 expressed in a mouse cortical collecting duct cell line. J Am Soc Nephrol 2000; 11:828-834.
68. Liu L, Hering-Smith KS, Schiro FR, et al. Serine protease activity in m-1 cortical collecting duct cells. Hypertension 2002; 39:860-864.
69. + channels. Am J Physiol Cell Physiol 2004; 286:C190-C194. Studies in fibroblasts expressing all three ENaC subunits suggest that most channels at the cell membrane are closed and thus inactive. Addition of extracellular trypsin, which mimics the effect of CAP/prostasin, activates silent channels by increasing their open probability.
70. Adachi M, Kitamura K, Miyoshi T, et al. Activation of epithelial sodium channels by prostasin in Xenopus oocytes. J Am Soc Nephrol 2001; 12:1114-1121.
71. Vuagniaux G, Vallet V, Jaeger NF, et al. Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus oocytes. J Gen Physiol 2002; 120:191-201.
72. Vallet V, Pfister C, Loffing J, et al. Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte. J Am Soc Nephrol 2002; 13:588-594.
73. Narikiyo T, Kitamura K, Adachi M, et al. Regulation of prostasin by aldosterone in the kidney. J Clin Invest 2002; 109:401-408.
74. Kemendy AE, Kleyman TR, Eaton DC. Aldosterone alters the open probability of amiloride-blockable sodium channels in A6 epithelia. Am J Physiol Cell Physiol 1992; 263:C825-C837.