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Genomes and Genes | Peter M SnyderSummaryAffiliation: University of Iowa Country: USA Publications
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cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2Peter M Snyder
Department of Internal Medicine, and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 279:45753-8. 2004..The data suggest that cAMP regulates ENaC in part by phosphorylation and inhibition of Nedd4-2. Moreover, Nedd4-2 is a central convergence point for kinase regulation of Na(+) transport...
Gating induces a conformational change in the outer vestibule of ENaCP M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Gen Physiol 116:781-90. 2000..Disruption of this mechanism could be important clinically since one of the mutations that increased Na(+) current (gamma(N530K)) was identified in a patient with renal disease...- Liddle's syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na(+) channel to the cell surfaceP M Snyder
200K Eckstein Medical Research Building, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Clin Invest 105:45-53. 2000..This sequence is the target for mutations that cause Liddle's syndrome, suggesting that cAMP-mediated translocation of ENaC to the cell surface is defective in this genetic form of hypertension... - A pore segment in DEG/ENaC Na(+) channelsP M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 274:28484-90. 1999..This segment contains a structural element ((S/G)CS) involved in selectivity of ENaC. The results are not consistent with predictions from the K(+) channel pore, suggesting that DEG/ENaC Na(+) channels have a novel pore structure... - The epithelial Na+ channel: cell surface insertion and retrieval in Na+ homeostasis and hypertensionPeter M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, 52422
Endocr Rev 23:258-75. 2002..Both hormones increase the expression of ENaC at the cell surface. The goal of this review is to summarize recent data on the regulation of ENaC expression at the cell surface... - Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathwaysRuifeng Zhou
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
J Biol Chem 285:30523-30. 2010..In contrast, Hrs-ΔUIM had no effect on degradation of uncleaved inactive channels. The data support a model in which Nedd4-2 induces binding of ENaC to Hrs, which mediates the sorting decision between ENaC degradation and recycling... - Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradationRuifeng Zhou
Department of Internal Medicine and Physiology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 280:4518-23. 2005..Conversely, phosphorylation increases Nedd4-2-mediated degradation of SGK. Thus, by phosphorylating Nedd4-2, SGK induces its own degradation. This feedback inhibition may fine-tune the regulation of epithelial Na+ absorption... - Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaCRuifeng Zhou
Departments of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA
J Biol Chem 282:20207-12. 2007..Together, the data suggest a model in which Nedd4-2 binds to and ubiquitinates ENaC at the cell surface, which targets surface ENaC for degradation, and thus, reduces epithelial Na(+) transport... 
Nedd4-2 induces endocytosis and degradation of proteolytically cleaved epithelial Na+ channelsRajesh Kabra
Departments of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA 52242, USA
J Biol Chem 283:6033-9. 2008..Together the data indicate that Nedd4-2 reduces ENaC surface expression by altering its trafficking at two distinct sites in the endocytic pathway, inducing endocytosis of cleaved channels and targeting them for degradation...- Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channelPeter M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 277:5-8. 2002..These data suggest that SGK regulates epithelial Na+ absorption in part by modulating the function of hNedd4-2... - Alternate promoters and variable splicing lead to hNedd4-2 isoforms with a C2 domain and varying number of WW domainsOmar A Itani
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA
Am J Physiol Renal Physiol 285:F916-29. 2003..Understanding the function of variant proteins will increase our knowledge of the role of hNedd4-2 in the regulation of ENaC and define protein domains important for Nedd4-2 function... - Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9)Vikas Sharotri
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 287:19266-74. 2012..By reducing ENaC channel number, PCSK9 could modulate epithelial Na(+) absorption, a major contributor to blood pressure control... - An evolutionarily conserved N-terminal Sgk1 variant with enhanced stability and improved functionNandita S Raikwar
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA, USA
Am J Physiol Renal Physiol 295:F1440-8. 2008..Together, the data demonstrate that a conserved NH2-terminal variant of Sgk1 shows improved stability, enhanced membrane association, and greater stimulation of epithelial Na+ transport in a heterologous expression system... - Extracellular chloride regulates the epithelial sodium channelDaniel M Collier
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
J Biol Chem 284:29320-5. 2009..Together, the data indicate that extracellular Cl(-) regulates ENaC activity, providing a potential mechanism by which changes in extracellular Cl(-) might modulate epithelial Na+ absorption... - Liddle's syndrome mutations increase Na+ transport through dual effects on epithelial Na+ channel surface expression and proteolytic cleavageKristin K Knight
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Proc Natl Acad Sci U S A 103:2805-8. 2006.... - Extracellular protons regulate human ENaC by modulating Na+ self-inhibitionDaniel M Collier
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
J Biol Chem 284:792-8. 2009..Together, the data support a model in which protons modulate ENaC gating by relieving Na(+) self-inhibition. We speculate that this may be an important mechanism to facilitate epithelial Na(+) transport under conditions of acidosis... - Intracellular sodium regulates proteolytic activation of the epithelial sodium channelKristin K Knight
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
J Biol Chem 283:27477-82. 2008.... - Relative contribution of Nedd4 and Nedd4-2 to ENaC regulation in epithelia determined by RNA interferencePeter M Snyder
Department of Internal Medicine and Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 279:5042-6. 2004..Thus, endogenous Nedd4-2 negatively regulates ENaC in epithelia and is a component of a signaling pathway by which steroid hormones regulate ENaC. Defects in this regulation may contribute to the pathogenesis of hypertension... - Oxidant regulated inter-subunit disulfide bond formation between ASIC1a subunitsXiang ming Zha
Howard Hughes Medical Institute and Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Proc Natl Acad Sci U S A 106:3573-8. 2009..They also suggest a mechanism by which the redox state can dynamically regulate membrane protein activity by forming intracellular bridges... - Identification of epithelial Na+ channel (ENaC) intersubunit Cl- inhibitory residues suggests a trimeric alpha gamma beta channel architectureDaniel M Collier
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 286:6027-32. 2011.... - Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channelF J McDonald
Department of Internal Medicine, Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA
Am J Physiol 268:C1157-63. 1995.... - Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase Nedd4-2Peter M Snyder
Department of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
Sci Signal 2:pe41. 2009..Nedd4-2 phosphorylation is emerging as a central convergence point for the regulation of epithelial Na(+) transport... - Multiple WW domains, but not the C2 domain, are required for inhibition of the epithelial Na+ channel by human Nedd4P M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 276:28321-6. 2001..Moreover, inhibition was decreased by mutation of WW domain 2 or WW domain 4. Thus, WW domains 2-4 each participate in the functional interaction between hNedd4 and ENaC in intact cells... - DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperatureC C Askwith
Department of Internal Medicine and Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Proc Natl Acad Sci U S A 98:6459-63. 2001..The finding that cold temperature modulates DEG/ENaC channel function may provide a molecular explanation for the widely recognized ability of temperature to modify taste sensation and mechanosensation... - Cloning and expression of a novel human brain Na+ channelM P Price
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
J Biol Chem 271:7879-82. 1996..Thus, BNC1 is the first cloned member of a new subfamily of mammalian Na+ channels. The function of BNC1 as a non-voltage-gated Na+ channel in human brain suggests it may play a novel role in neurotransmission... - Membrane topology of the amiloride-sensitive epithelial sodium channelP M Snyder
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
J Biol Chem 269:24379-83. 1994..Because of their sequence similarity, it is likely that this structure is shared by other ENaC subunits and possibly the degenerins of Caenorhabditis elegans as well... - Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2Peijun P Shi
Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, USA
Am J Physiol Renal Physiol 295:F462-70. 2008..The absence of this gene is sufficient to produce salt-sensitive hypertension. This model provides an opportunity to further investigate mechanisms and consequences of this common disorder... - Heteromultimers of DEG/ENaC subunits form H+-gated channels in mouse sensory neuronsChristopher J Benson
Department of Internal Medicine and Psychiatry, and Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Proc Natl Acad Sci U S A 99:2338-43. 2002..These data indicate that combinations of two or more DEG/ENaC subunits coassemble as heteromultimers to generate transient H(+)-gated currents in mouse DRG neurons... - Regulation of epithelial sodium channel activity through a region of the carboxyl terminus of the alpha -subunit. Evidence for intracellular kinase-mediated reactionsK A Volk
Department of Internal Medicine, University of Iowa College of Medicine and the Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA
J Biol Chem 276:43887-93. 2001..This region is potentially important in effecting kinase-mediated increases in ENaC activity... - Minireview: regulation of epithelial Na+ channel traffickingPeter M Snyder
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, 52242, USA
Endocrinology 146:5079-85. 2005..Thus, aldosterone and vasopressin regulate epithelial Na(+) transport in part by altering ENaC trafficking to and from the cell surface... - Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channelF J McDonald
Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
Am J Physiol 266:L728-34. 1994..Expression of alpha hENaC in Xenopus oocytes produced currents that were amiloride sensitive and Na+ selective, properties consistent with the function of epithelial Na+ channels in native tissues... - Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptorSudha K Shenoy
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Biol Chem 283:22166-76. 2008..Collectively, our findings indicate that the degradative fate of the beta(2)AR in the lysosomal compartments is dependent upon beta-arrestin2-mediated recruitment of Nedd4 to the activated receptor and Nedd4-catalyzed ubiquitination... - The kidney-specific WNK1 isoform is induced by aldosterone and stimulates epithelial sodium channel-mediated Na+ transportAniko Naray-Fejes-Toth
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA
Proc Natl Acad Sci U S A 101:17434-9. 2004..These observations suggest that stimulation of KS-WNK1 expression might be an important element of aldosterone-induced Na(+) retention and hypertension... - A region directly following the second transmembrane domain in gamma ENaC is required for normal channel gatingRachell E Booth
Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78229, USA
J Biol Chem 278:41367-79. 2003..Similar to deletion of Gln573-Pro600, deletion of Gln573-Arg583 but not Thr584-Pro600 decreased ENaC activity. The current results demonstrate that residues within Gln573-Arg583 of gammaENaC are necessary for normal channel gating... - Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channelFiona J McDonald
Department of Physiology, University of Otago, Dunedin 9100, New Zealand
Am J Physiol Renal Physiol 283:F431-6. 2002..Thus expression, binding, and functional data all suggest that WWP2 is a candidate to regulate ENaC-mediated Na(+) transport in epithelia...