Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pflugers Arch
2012 Jun 01;4636:819-27. doi: 10.1007/s00424-012-1091-1.
Show Gene links
Show Anatomy links
Regulation of ENaC biogenesis by the stress response protein SERP1.
Faria D
,
Lentze N
,
Almaça J
,
Luz S
,
Alessio L
,
Tian Y
,
Martins JP
,
Cruz P
,
Schreiber R
,
Rezwan M
,
Farinha CM
,
Auerbach D
,
Amaral MD
,
Kunzelmann K
.
???displayArticle.abstract???
Cystic fibrosis lung disease is caused by reduced Cl(-) secretion along with enhanced Na(+) absorption, leading to reduced airway surface liquid and compromised mucociliary clearance. Therapeutic strategies have been developed to activate cystic fibrosis transmembrane conductance regulator (CFTR) or to overcome enhanced Na(+) absorption by the epithelial Na(+) channel (ENaC). In a split-ubiquitin-based two-hybrid screening, we identified stress-associated ER protein 1 (SERP1)/ribosome-associated membrane protein 4 as a novel interacting partner for the ENaC β-subunit. SERP1 is induced during cell stress and interacts with the molecular chaperone calnexin, thus controlling early biogenesis of membrane proteins. ENaC activity was measured in the human airway epithelial cell lines H441 and A549 and in voltage clamp experiments with ENaC-overexpressing Xenopus oocytes. We found that expression of SERP1 strongly inhibits amiloride-sensitive Na(+) transport. SERP1 coimmunoprecipitated and colocalized with βENaC in the endoplasmic reticulum, together with the chaperone calnexin. In contrast to the inhibitory effects on ENaC, SERP1 appears to promote expression of CFTR. Taken together, SERP1 is a novel cochaperone and regulator of ENaC expression.
Almaça,
AMPK controls epithelial Na(+) channels through Nedd4-2 and causes an epithelial phenotype when mutated.
2009, Pubmed
Almaça,
AMPK controls epithelial Na(+) channels through Nedd4-2 and causes an epithelial phenotype when mutated.
2009,
Pubmed
Amaral,
Molecular targeting of CFTR as a therapeutic approach to cystic fibrosis.
2007,
Pubmed
Bebök,
The mechanism underlying cystic fibrosis transmembrane conductance regulator transport from the endoplasmic reticulum to the proteasome includes Sec61beta and a cytosolic, deglycosylated intermediary.
1998,
Pubmed
Boucher,
Evidence for airway surface dehydration as the initiating event in CF airway disease.
2007,
Pubmed
Bouvry,
Hypoxia-induced cytoskeleton disruption in alveolar epithelial cells.
2006,
Pubmed
Bruscia,
Isolation of CF cell lines corrected at DeltaF508-CFTR locus by SFHR-mediated targeting.
2002,
Pubmed
Butterworth,
Regulation of the epithelial sodium channel by membrane trafficking.
2009,
Pubmed
Carpenter,
Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expression.
2003,
Pubmed
Chang,
Role of N-linked oligosaccharides in the biosynthetic processing of the cystic fibrosis membrane conductance regulator.
2008,
Pubmed
Dinudom,
Nedd4 mediates control of an epithelial Na+ channel in salivary duct cells by cytosolic Na+.
1998,
Pubmed
Farinha,
Most F508del-CFTR is targeted to degradation at an early folding checkpoint and independently of calnexin.
2005,
Pubmed
Favaloro,
Distinct targeting pathways for the membrane insertion of tail-anchored (TA) proteins.
2008,
Pubmed
French,
Colocalization of fluorescent markers in confocal microscope images of plant cells.
2008,
Pubmed
Gaillard,
Regulation of the epithelial Na+ channel and airway surface liquid volume by serine proteases.
2010,
Pubmed
Glozman,
N-glycans are direct determinants of CFTR folding and stability in secretory and endocytic membrane traffic.
2009,
Pubmed
Goralski,
Osmolytes and ion transport modulators: new strategies for airway surface rehydration.
2010,
Pubmed
Güney,
Dexamethasone prevents transport inhibition by hypoxia in rat lung and alveolar epithelial cells by stimulating activity and expression of Na+-K+-ATPase and epithelial Na+ channels.
2007,
Pubmed
Hopf,
Cystic fibrosis transmembrane conductance regulator inhibits epithelial Na+ channels carrying Liddle's syndrome mutations.
1999,
Pubmed
,
Xenbase
Hughey,
Distinct pools of epithelial sodium channels are expressed at the plasma membrane.
2004,
Pubmed
,
Xenbase
Jain,
Effects of hypoxia on the alveolar epithelium.
2005,
Pubmed
Kamynina,
A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel.
2001,
Pubmed
,
Xenbase
Kongsuphol,
Mechanistic insight into control of CFTR by AMPK.
2009,
Pubmed
Kunzelmann,
Purinergic inhibition of the epithelial Na+ transport via hydrolysis of PIP2.
2005,
Pubmed
,
Xenbase
Lentze,
Membrane-based yeast two-hybrid system to detect protein interactions.
2008,
Pubmed
Mairbäurl,
Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia.
1997,
Pubmed
Mall,
The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.
1998,
Pubmed
Mall,
Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice.
2004,
Pubmed
Planès,
Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells.
2002,
Pubmed
Pool,
A trans-membrane segment inside the ribosome exit tunnel triggers RAMP4 recruitment to the Sec61p translocase.
2009,
Pubmed
Rosser,
Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.
2008,
Pubmed
Snyder,
Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel.
2002,
Pubmed
Stagljar,
A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo.
1998,
Pubmed
Thome,
Modulation of sodium transport in fetal alveolar epithelial cells by oxygen and corticosterone.
2003,
Pubmed
Wang,
Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis.
2006,
Pubmed
Wodopia,
Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung.
2000,
Pubmed
Yamaguchi,
Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation.
1999,
Pubmed
