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Regulation of the epithelial Na+ channel by paraoxonase-2.
Shi S
,
Buck TM
,
Kinlough CL
,
Marciszyn AL
,
Hughey RP
,
Chalfie M
,
Brodsky JL
,
Kleyman TR
.
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Paraoxonase-2 (PON-2) is a membrane-bound lactonase with unique anti-oxidative and anti-atherosclerotic properties. PON-2 shares key structural elements with MEC-6, an endoplasmic reticulum-resident molecular chaperone in Caenorhabditis elegans MEC-6 modulates the expression of a mechanotransductive ion channel comprising MEC-4 and MEC-10 in touch-receptor neurons. Because pon-2 mRNA resides in multiple rat nephron segments, including the aldosterone-sensitive distalnephron where the epithelial Na+ channel (ENaC) is expressed, we hypothesized that PON-2 would similarly regulate ENaC expression. We observed PON-2 expression in aquaporin 2-positive principal cells of the distalnephron of adult human kidney. PON-2 also co-immunoprecipitated with ENaC when co-expressed in HEK293 cells. When PON-2 was co-expressed with ENaC in Xenopus oocytes, ENaC activity was reduced, reflecting a reduction in ENaC surface expression. MEC-6 also reduced ENaC activity when co-expressed in Xenopus oocytes. The PON-2 inhibitory effect was ENaC-specific, as PON-2 had no effect on functional expression of the renal outer medullary potassium channel. PON-2 did not alter the response of ENaC to extracellular Na+, mechanical shear stress, or α-chymotrypsin-mediated proteolysis, suggesting that PON-2 did not alter the regulation of ENaC by these factors. Together, our data suggest that PON-2 regulates ENaC activity by modulating its intracellular trafficking and surface expression.
Altenhöfer,
One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity.
2010, Pubmed
Altenhöfer,
One enzyme, two functions: PON2 prevents mitochondrial superoxide formation and apoptosis independent from its lactonase activity.
2010,
Pubmed
Althaus,
Mechano-sensitivity of epithelial sodium channels (ENaCs): laminar shear stress increases ion channel open probability.
2007,
Pubmed
,
Xenbase
Bhalla,
Mechanisms of ENaC regulation and clinical implications.
2008,
Pubmed
Brown,
Antigen retrieval in cryostat tissue sections and cultured cells by treatment with sodium dodecyl sulfate (SDS).
1996,
Pubmed
Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase
Buck,
The Lhs1/GRP170 chaperones facilitate the endoplasmic reticulum-associated degradation of the epithelial sodium channel.
2013,
Pubmed
,
Xenbase
Buck,
Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein.
2017,
Pubmed
Buck,
The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones.
2010,
Pubmed
,
Xenbase
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Carattino,
Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation.
2008,
Pubmed
,
Xenbase
Carattino,
The epithelial Na+ channel is inhibited by a peptide derived from proteolytic processing of its alpha subunit.
2006,
Pubmed
,
Xenbase
Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
Pubmed
,
Xenbase
Carattino,
Prostasin interacts with the epithelial Na+ channel and facilitates cleavage of the γ-subunit by a second protease.
2014,
Pubmed
,
Xenbase
Chalfie,
Neurosensory mechanotransduction.
2009,
Pubmed
Chanoux,
Hsc70 negatively regulates epithelial sodium channel trafficking at multiple sites in epithelial cells.
2013,
Pubmed
,
Xenbase
Chanoux,
Hsp70 promotes epithelial sodium channel functional expression by increasing its association with coat complex II and its exit from endoplasmic reticulum.
2012,
Pubmed
,
Xenbase
Chelur,
The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.
2002,
Pubmed
,
Xenbase
Chen,
Subunit composition of a DEG/ENaC mechanosensory channel of Caenorhabditis elegans.
2015,
Pubmed
,
Xenbase
Chen,
Caenorhabditis elegans paraoxonase-like proteins control the functional expression of DEG/ENaC mechanosensory proteins.
2016,
Pubmed
,
Xenbase
Cortes-González,
Opposite effect of Hsp90α and Hsp90β on eNOS ability to produce nitric oxide or superoxide anion in human embryonic kidney cells.
2010,
Pubmed
Devarajan,
Paraoxonase 2 deficiency alters mitochondrial function and exacerbates the development of atherosclerosis.
2011,
Pubmed
Devarajan,
Inflammation, infection, cancer and all that…the role of paraoxonases.
2014,
Pubmed
Driscoll,
The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration.
1991,
Pubmed
Duc,
Cell-specific expression of epithelial sodium channel alpha, beta, and gamma subunits in aldosterone-responsive epithelia from the rat: localization by in situ hybridization and immunocytochemistry.
1994,
Pubmed
Fushimi,
Cloning and expression of apical membrane water channel of rat kidney collecting tubule.
1993,
Pubmed
,
Xenbase
Goldfarb,
Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels.
2006,
Pubmed
,
Xenbase
Grifoni,
Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration.
2008,
Pubmed
Grumbach,
ERp29 regulates epithelial sodium channel functional expression by promoting channel cleavage.
2014,
Pubmed
,
Xenbase
Gu,
Genetic interactions affecting touch sensitivity in Caenorhabditis elegans.
1996,
Pubmed
Hagmann,
Breaking the chain at the membrane: paraoxonase 2 counteracts lipid peroxidation at the plasma membrane.
2014,
Pubmed
Harel,
Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes.
2004,
Pubmed
Hoger,
Shear stress regulates the endothelial Kir2.1 ion channel.
2002,
Pubmed
,
Xenbase
Horke,
Paraoxonase-2 reduces oxidative stress in vascular cells and decreases endoplasmic reticulum stress-induced caspase activation.
2007,
Pubmed
Horke,
Protective effect of paraoxonase-2 against endoplasmic reticulum stress-induced apoptosis is lost upon disturbance of calcium homoeostasis.
2008,
Pubmed
Huang,
Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.
1994,
Pubmed
Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
Pubmed
,
Xenbase
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Johnson,
Evolution and function of diverse Hsp90 homologs and cochaperone proteins.
2012,
Pubmed
Kashlan,
Small heat shock protein alphaA-crystallin regulates epithelial sodium channel expression.
2007,
Pubmed
,
Xenbase
Kashlan,
Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.
2012,
Pubmed
Kashlan,
ENaC structure and function in the wake of a resolved structure of a family member.
2011,
Pubmed
Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed
Kellenberger,
International Union of Basic and Clinical Pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.
2015,
Pubmed
Kleyman,
ENaC at the cutting edge: regulation of epithelial sodium channels by proteases.
2009,
Pubmed
Lee,
Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes.
2015,
Pubmed
Levy,
Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats.
2007,
Pubmed
Ma,
Anionic phospholipids regulate native and expressed epithelial sodium channel (ENaC).
2002,
Pubmed
,
Xenbase
Maarouf,
Novel determinants of epithelial sodium channel gating within extracellular thumb domains.
2009,
Pubmed
,
Xenbase
Mack,
Engineering and Evolution of Molecular Chaperones and Protein Disaggregases with Enhanced Activity.
2016,
Pubmed
Mackness,
Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins.
1996,
Pubmed
Mochizuki,
Human PON2 gene at 7q21.3: cloning, multiple mRNA forms, and missense polymorphisms in the coding sequence.
1998,
Pubmed
Morimoto,
Mechanism underlying flow stimulation of sodium absorption in the mammalian collecting duct.
2006,
Pubmed
,
Xenbase
Ng,
Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein.
2001,
Pubmed
Ng,
Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2.
2006,
Pubmed
O'Hagan,
The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals.
2005,
Pubmed
Passero,
TMPRSS4-dependent activation of the epithelial sodium channel requires cleavage of the γ-subunit distal to the furin cleavage site.
2012,
Pubmed
,
Xenbase
Pochynyuk,
Identification of a functional phosphatidylinositol 3,4,5-trisphosphate binding site in the epithelial Na+ channel.
2005,
Pubmed
Prince,
Cell surface expression and biosynthesis of epithelial Na+ channels.
1998,
Pubmed
Shi,
ENaC regulation by proteases and shear stress.
2013,
Pubmed
Staub,
Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination.
1997,
Pubmed
,
Xenbase
Stockand,
Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure.
2008,
Pubmed
Stoltz,
A common mutation in paraoxonase-2 results in impaired lactonase activity.
2009,
Pubmed
Valentijn,
Biosynthesis and processing of epithelial sodium channels in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Vila-Carriles,
Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells.
2007,
Pubmed
Vuagniaux,
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.
2002,
Pubmed
,
Xenbase
Warnock,
Blood pressure and amiloride-sensitive sodium channels in vascular and renal cells.
2014,
Pubmed
Yang,
Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase.
2012,
Pubmed
You,
Derlin-1 promotes ubiquitylation and degradation of the epithelial Na+ channel, ENaC.
2017,
Pubmed
Zhou,
Mutations in the pore region of ROMK enhance Ba2+ block.
1996,
Pubmed
,
Xenbase