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Genomes and Genes
Species | Scnn1gSummaryGene Symbol: Scnn1g Description: sodium channel, nonvoltage-gated 1 gamma Alias: SCNEG, amiloride-sensitive sodium channel subunit gamma, ENaC gamma, epithelial Na(+) channel subunit gamma, gamma-ENaC, gamma-NaCH, nonvoltage-gated sodium channel 1 subunit gamma Species: mouse Products: Scnn1g Top Publications
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Publications
- Carattino M, Mueller G, Palmer L, Frindt G, Rued A, Hughey R, et al. Prostasin interacts with the epithelial Na+ channel and facilitates cleavage of the γ-subunit by a second protease. Am J Physiol Renal Physiol. 2014;307:F1080-7 pubmed publisher..Our results suggest that the inhibitory tract dissociates from the γ-subunit in kidneys from rats on a low-Na+ diet. ..
- Perlewitz A, Nafz B, Skalweit A, Fähling M, Persson P, Thiele B. Aldosterone and vasopressin affect {alpha}- and {gamma}-ENaC mRNA translation. Nucleic Acids Res. 2010;38:5746-60 pubmed publisher..Immunoprecipitation and UV-crosslinking analysis of ?-ENaC-mRNA/HuR complexes document the significance of ?-ENaC-mRNA-3'-UTR/HuR interaction for hormonal control of ENaC synthesis...
- Rossier B, Staub O, Hummler E. Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: importance in the control of blood pressure and hypertension. FEBS Lett. 2013;587:1929-41 pubmed publisher..This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics. ..
- Fotia A, Dinudom A, Shearwin K, Koch J, Korbmacher C, Cook D, et al. The role of individual Nedd4-2 (KIAA0439) WW domains in binding and regulating epithelial sodium channels. FASEB J. 2003;17:70-2 pubmed..These data suggest that Nedd4-2 WW3 and WW4 interact with distinct, noninterchangeable sites in ENaC and that to prevent Na+ feedback control of ENaC it is necessary to occlude both sites. ..
- Barker P, Nguyen M, Gatzy J, Grubb B, Norman H, Hummler E, et al. Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism. J Clin Invest. 1998;102:1634-40 pubmed..The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1. ..
- Edinger R, Lebowitz J, Li H, Alzamora R, Wang H, Johnson J, et al. Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:150-7 pubmed publisher..In summary, these results suggest a novel mode of ENaC regulation that occurs through IKKbeta-dependent Nedd4-2 phosphorylation at a recognized SGK1 and protein kinase A target site. ..
- Bruns J, Hu B, Ahn Y, Sheng S, Hughey R, Kleyman T. Multiple epithelial Na+ channel domains participate in subunit assembly. Am J Physiol Renal Physiol. 2003;285:F600-9 pubmed..These data suggest that multiple sites within the alpha-subunit participate in subunit-subunit interactions that are required for proper assembly of the heterooligomeric ENaC complex. ..
- Harvey K, Dinudom A, Cook D, Kumar S. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001;276:8597-601 pubmed..We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or function in a tissue- and/or signal-specific manner to down-regulate ENaC. ..
- Staruschenko A, Medina J, Patel P, Shapiro M, Booth R, Stockand J. Fluorescence resonance energy transfer analysis of subunit stoichiometry of the epithelial Na+ channel. J Biol Chem. 2004;279:27729-34 pubmed..The current results as a whole, thus, are most consistent with a higher ordered channel possibly with a 3alpha:3beta:3gamma stoichiometry. ..
- Guipponi M, Vuagniaux G, Wattenhofer M, Shibuya K, Vazquez M, Dougherty L, et al. The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro. Hum Mol Genet. 2002;11:2829-36 pubmed
- Toivola D, Krishnan S, Binder H, Singh S, Omary M. Keratins modulate colonocyte electrolyte transport via protein mistargeting. J Cell Biol. 2004;164:911-21 pubmed..Therefore, colonic keratins have a novel function in regulating electrolyte transport, likely by targeting ion transporters to their cellular compartments. ..
- Wakida N, Kitamura K, Tuyen D, Maekawa A, Miyoshi T, Adachi M, et al. Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone. Kidney Int. 2006;70:1432-8 pubmed..PN-1 could represent a new factor that contributes to regulation of ENaC activity in the kidney. ..
- Takahashi N, Smithies O. Gene targeting approaches to analyzing hypertension. J Am Soc Nephrol. 1999;10:1598-605 pubmed..These various gene targeting experiments help identify genes regulating BP, promote a better understanding of the pathophysiology of the condition, and help identify potential targets for therapies. ..
- Li J, Sheng S, Perry C, Kleyman T. Asymmetric organization of the pore region of the epithelial sodium channel. J Biol Chem. 2003;278:13867-74 pubmed..Our results, placed in context with previous observations, suggest that pore regions from the three ENaC subunits have an asymmetric organization. ..
- Butterworth M, Edinger R, Ovaa H, Burg D, Johnson J, Frizzell R. The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. J Biol Chem. 2007;282:37885-93 pubmed..This constitutes a novel function for UCH in epithelia and in the regulation of ion channels and demonstrates the dynamic regulation of apically located ENaC by recycling, which is facilitated by this DUB. ..
- Pearce L, Sommer E, Sakamoto K, Wullschleger S, Alessi D. Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochem J. 2011;436:169-79 pubmed publisher..Taken together, these results suggest that Protor-1 may play a role in enabling mTORC2 to efficiently activate SGK1, at least in the kidney. ..
- Rajagopal M, Kathpalia P, Widdicombe J, Pao A. Differential effects of extracellular ATP on chloride transport in cortical collecting duct cells. Am J Physiol Renal Physiol. 2012;303:F483-91 pubmed publisher..This interplay between aldosterone and purinergic signaling pathways may be relevant for regulating NaCl transport in cortical collecting duct cells under different states of extracellular fluid volume. ..
- Pradervand S, Barker P, Wang Q, Ernst S, Beermann F, Grubb B, et al. Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel. Proc Natl Acad Sci U S A. 1999;96:1732-7 pubmed
- Picard N, Eladari D, El Moghrabi S, Planes C, Bourgeois S, Houillier P, et al. Defective ENaC processing and function in tissue kallikrein-deficient mice. J Biol Chem. 2008;283:4602-11 pubmed..The results demonstrate that TK, like several other proteases, can activate ENaC in the kidney and the colon. ..
- Pochynyuk O, Bugaj V, Rieg T, Insel P, Mironova E, Vallon V, et al. Paracrine regulation of the epithelial Na+ channel in the mammalian collecting duct by purinergic P2Y2 receptor tone. J Biol Chem. 2008;283:36599-607 pubmed publisher..P2Y2 receptor activation by nucleotides thus provides physiologically important regulation of ENaC and electrolyte handling in mammalian kidney. ..
- Pandit M, Strait K, Matsuda T, Kohan D. Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production. Am J Physiol Renal Physiol. 2012;302:F1325-30 pubmed publisher..This constitutes the first report of either ENaC or mitochondrial NCX regulation of an autocrine factor in any biologic system. ..
- Mérillat A, Charles R, Porret A, Maillard M, Rossier B, Beermann F, et al. Conditional gene targeting of the ENaC subunit genes Scnn1b and Scnn1g. Am J Physiol Renal Physiol. 2009;296:F249-56 pubmed publisher..Since complete gene inactivation of the beta- and gamma-ENaC subunit genes (Scnn1b and Scnn1g) leads to early postnatal death, we generated conditional alleles and obtained mice harboring floxed and null ..
- Brooker D, Kozak C, Kleyman T. Epithelial sodium channel genes Scnn1b and Scnn1g are closely linked on distal mouse chromosome 7. Genomics. 1995;29:784-6 pubmedThe chromosomal localizations of Scnn1b and Scnn1g, genes corresponding to the beta- and gamma-subunits, respectively, of an epithelial non-voltage-gated amiloride-sensitive sodium channel, were determined by analyses of two sets of ..
- Hansson J, Nelson Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995;11:76-82 pubmed
- Li X, Zhou F, Marcus D, Wangemann P. Endolymphatic Na? and K? concentrations during cochlear growth and enlargement in mice lacking Slc26a4/pendrin. PLoS ONE. 2013;8:e65977 pubmed publisher..The data suggest that the endolymphatic enlargement caused by a loss of Slc26a4 is a consequence of disrupted Na(+) transport...
- Nakamura K, Stokes J, McCray P. Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung. Am J Physiol Cell Physiol. 2002;283:C762-72 pubmed
- Jernigan N, Drummond H. Vascular ENaC proteins are required for renal myogenic constriction. Am J Physiol Renal Physiol. 2005;289:F891-901 pubmed
- Fejes Toth G, Frindt G, NARAY FEJES TOTH A, Palmer L. Epithelial Na+ channel activation and processing in mice lacking SGK1. Am J Physiol Renal Physiol. 2008;294:F1298-305 pubmed publisher..These results indicated that SGK1 is essential for optimal processing of ENaC but is not required for activation of the channel by aldosterone. ..
- Pavlov T, Levchenko V, Staruschenko A. Role of Rho GDP dissociation inhibitor α in control of epithelial sodium channel (ENaC)-mediated sodium reabsorption. J Biol Chem. 2014;289:28651-9 pubmed publisher..We conclude that changes in the RhoGDIα-dependent pathway have a permissive role in the Rac1-mediated enhancement of ENaC activity observed in salt-induced hypertension. ..
- Lovgren A, Kovarova M, Koller B. cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis. Mol Cell Biol. 2007;27:4416-30 pubmed
- Shi S, Carattino M, Kleyman T. Role of the wrist domain in the response of the epithelial sodium channel to external stimuli. J Biol Chem. 2012;287:44027-35 pubmed publisher..Mutants that exhibited reduced inhibition by external Na(+) also showed an enhanced response to shear stress. Together, our data suggest that the wrist domain has a role in modulating the channel's response to external stimuli...
- Shi S, Kleyman T. Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block. Am J Physiol Renal Physiol. 2013;305:F1585-92 pubmed publisher..In summary, we have identified novel pore-lining residues of the ?-subunit of ENaC that are important for proper channel gating and its interaction with amiloride. ..
- Pathak B, Shaughnessy J, Meneton P, Greeb J, Shull G, Jenkins N, et al. Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene. Genomics. 1996;33:124-7 pubmedThe amiloride-sensitive epithelial sodium channel alpha, beta, and gamma subunit genes, Scnn1a, Scnn1b, and Scnn1g, and the thiazide-sensitive sodium chloride cotransporter gene, Slc12a1, have been mapped in the mouse using an ..
- Li K, Guo D, Zhu H, Hering Smith K, Hamm L, Ouyang J, et al. Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells. Am J Physiol Regul Integr Comp Physiol. 2010;299:R590-5 pubmed publisher..6 +/- 0.2 to 4.9 +/- 0.2 muA/cm(2) (P < 0.01). This study has identified a novel function of IL-6, namely, IL-6 may activate ENaC. Therefore, renal inflammation mediated by IL-6 likely contributes to impaired pressure natriuresis. ..
- Bertog M, Cuffe J, Pradervand S, Hummler E, Hartner A, Porst M, et al. Aldosterone responsiveness of the epithelial sodium channel (ENaC) in colon is increased in a mouse model for Liddle's syndrome. J Physiol. 2008;586:459-75 pubmed..Aldosterone-induced transcriptional up-regulation of the channel's beta- and gamma-subunit (beta ENaC and gamma ENaC) and of the serum- and glucocorticoid-inducible kinase 1 (SGK1) was similar in colon tissue from Liddle and wild-..
- Hughey R, Bruns J, Kinlough C, Harkleroad K, Tong Q, Carattino M, et al. Epithelial sodium channels are activated by furin-dependent proteolysis. J Biol Chem. 2004;279:18111-4 pubmed..Channel activity in furin-deficient cells was rescued by expression of furin. Our data provide the first example of a vertebrate ion channel that is a substrate for furin and whose activity is dependent on its proteolysis. ..
- Mohan S, Bruns J, Weixel K, Edinger R, Bruns J, Kleyman T, et al. Differential current decay profiles of epithelial sodium channel subunit combinations in polarized renal epithelial cells. J Biol Chem. 2004;279:32071-8 pubmed
- Jernigan N, Drummond H. Myogenic vasoconstriction in mouse renal interlobar arteries: role of endogenous beta and gammaENaC. Am J Physiol Renal Physiol. 2006;291:F1184-91 pubmed..Our results provide the first direct evidence that beta and gammaENaC proteins are essential in mediating myogenic vasoconstriction in mouse renal interlobar arteries. ..
- Tsang L, Chan L, Chan H. Altered cyclic expression of epithelial Na+ channel subunits and cystic fibrosis transmembrane conductance regulator in mouse endometrium by a low sodium diet. Cell Biol Int. 2004;28:549-55 pubmed..The altered cyclic expression of uterine ENaC and CFTR by a low sodium diet suggests that these ion channels may be affected by elevated circulating aldosterone, which may disrupt reproductive events in the uterus. ..
- Crawshaw L, Wallace H, Christensen R, Crabbe J. Influence of ethanol on thermoregulation: mapping quantitative trait loci. Physiol Genomics. 2001;7:159-69 pubmed..To our knowledge, this is the first report of QTLs that underlie changes in regulation as well as the disruption of a physiological regulatory system. ..
- Kim S, Kim K, Raveendran N, Wu T, Pondugula S, Marcus D. Regulation of ENaC-mediated sodium transport by glucocorticoids in Reissner's membrane epithelium. Am J Physiol Cell Physiol. 2009;296:C544-57 pubmed publisher..These results provide an understanding and a molecular definition of an important transport function of Reissner's membrane epithelium in the homeostasis of cochlear endolymph...
- Sugiyama F, Churchill G, Li R, Libby L, Carver T, Yagami K, et al. QTL associated with blood pressure, heart rate, and heart weight in CBA/CaJ and BALB/cJ mice. Physiol Genomics. 2002;10:5-12 pubmed..Identification of the genes for these QTL should lead to a better understanding of the causes of essential hypertension. ..
- Xu Y, Wang Y, Besnard V, Ikegami M, Wert S, Heffner C, et al. Transcriptional programs controlling perinatal lung maturation. PLoS ONE. 2012;7:e37046 pubmed publisher..The present study systemically mapped key regulators, bioprocesses, and transcriptional networks controlling lung maturation, providing the basis for new therapeutic strategies to enhance lung function in preterm infants. ..
- Edinger R, Bertrand C, Rondandino C, Apodaca G, Johnson J, Butterworth M. The epithelial sodium channel (ENaC) establishes a trafficking vesicle pool responsible for its regulation. PLoS ONE. 2012;7:e46593 pubmed publisher..These findings indicate that ENaC is not a passive passenger in regulated epithelial vesicle trafficking, but plays a role in establishing and maintaining the pool of vesicles that respond to cAMP stimulation...
- Pavlov T, Ilatovskaya D, Levchenko V, Li L, Ecelbarger C, Staruschenko A. Regulation of ENaC in mice lacking renal insulin receptors in the collecting duct. FASEB J. 2013;27:2723-32 pubmed publisher..This study provides new information about the importance of insulin receptors expressed in collecting duct principal cells for ENaC activity...
- Roos K, Bugaj V, Mironova E, Stockand J, Ramkumar N, Rees S, et al. Adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity. J Am Soc Nephrol. 2013;24:218-27 pubmed publisher..In summary, these data suggest that adenylyl cyclase VI mediates vasopressin-stimulated ENaC activity in the kidney...
- Maarouf A, Sheng N, Chen J, Winarski K, Okumura S, Carattino M, et al. Novel determinants of epithelial sodium channel gating within extracellular thumb domains. J Biol Chem. 2009;284:7756-65 pubmed publisher..Our results demonstrate that alphaGly(481) and gammaMet(438) are functional determinants of Na(+) self-inhibition and of ENaC gating and suggest that the thumb domain contributes to the channel gating machinery. ..
- Fotia A, Ekberg J, Adams D, Cook D, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004;279:28930-5 pubmed..Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na(v) channels in vivo. ..
- Sheng S, Maarouf A, Bruns J, Hughey R, Kleyman T. Functional role of extracellular loop cysteine residues of the epithelial Na+ channel in Na+ self-inhibition. J Biol Chem. 2007;282:20180-90 pubmed..We conclude that approximately half of the ECL Cys residues in the alpha and gamma ENaC subunits are required to establish the tertiary structure that ensures a proper Na(+) self-inhibition response, ..
- Lee I, Dinudom A, Sanchez Perez A, Kumar S, Cook D. Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2. J Biol Chem. 2007;282:29866-73 pubmed..Together these data suggest that both Akt and Sgk are components of an insulin signaling pathway that increases Na(+) absorption by up-regulating membrane expression of ENaC via a regulatory system that involves inhibition of Nedd4-2. ..
- Yang G, Nie H, Lu L, Chen J, Lu X, Ji H, et al. Estrogen regulates the expression and activity of epithelial sodium channel in mouse osteoblasts. Cell Mol Biol (Noisy-le-grand). 2011;57 Suppl:OL1480-6 pubmed..Our results suggest that estrogen regulates expression and function of ENaC in osteoblasts may provide a new clue that the mechanism of high dose of estrogen influence osteoblast bone formation via ENaC activity. ..
- Hernández González E, Sosnik J, Edwards J, Acevedo J, Mendoza Lujambio I, López González I, et al. Sodium and epithelial sodium channels participate in the regulation of the capacitation-associated hyperpolarization in mouse sperm. J Biol Chem. 2006;281:5623-33 pubmed..These results suggest that increases in cAMP content occurring during capacitation may inhibit ENaCs to produce a required hyperpolarization of the sperm membrane. ..
- Guan Y, Hao C, Cha D, Rao R, Lu W, Kohan D, et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med. 2005;11:861-6 pubmed..Treating cultured collecting ducts with TZDs increased amiloride-sensitive Na(+) absorption and Scnn1g mRNA (encoding the epithelial Na(+) channel ENaCgamma) expression through a PPARgamma-dependent pathway...
- Lazrak A, Chen L, Jurkuvenaite A, Doran S, Liu G, Li Q, et al. Regulation of alveolar epithelial Na+ channels by ERK1/2 in chlorine-breathing mice. Am J Respir Cell Mol Biol. 2012;46:342-54 pubmed publisher..The reactive intermediates formed during and after exposure to Cl(2) activated ERK1/2 in ATII cells in vitro and in vivo, leading to decreased ENaC concentrations and activity. ..
- Reisenauer M, Wang S, Xia Y, Zhang W. Dot1a contains three nuclear localization signals and regulates the epithelial Na+ channel (ENaC) at multiple levels. Am J Physiol Renal Physiol. 2010;299:F63-76 pubmed publisher..In brief, Dot1a and AF9 downregulate Na(+) transport, most likely by regulating ENaC mRNA and subsequent protein expression and ENaC activity. ..
- Harvey K, Dinudom A, Komwatana P, Jolliffe C, Day M, Parasivam G, et al. All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+. J Biol Chem. 1999;274:12525-30 pubmed..We propose that Nedd4-mediated down-regulation of Na+ channels involves the binding of WW domains 2 and 3 to the Na+ channel and of WW domain 1 to an unknown associated protein. ..