{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:05:45Z","timestamp":1791219945352,"version":"4.1.0"},"reference-count":106,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:p>The epithelial Na+ channel (ENaC) is a pathway for Na+ transport across epithelia, including the kidney collecting duct, lung, and distal colon. ENaC is critical for Na+ homeostasis and blood pressure control; defects in ENaC function and regulation are responsible for inherited forms of hypertension and hypotension and may contribute to the pathogenesis of cystic fibrosis and other lung diseases. An emerging theme is that epithelial Na+ transport is regulated in large part through trafficking mechanisms that control ENaC expression at the cell surface. ENaC trafficking is regulated at multiple steps. Delivery of channels to the cell surface is regulated by aldosterone (and corticosteroids) and vasopressin, which increase ENaC synthesis and exocytosis, respectively. Conversely, endocytosis and degradation is controlled by a sequence located in the C terminus of \u03b1, \u03b2, and \u03b3ENaC (PPPXYXXL). This sequence functions as an endocytosis motif and as a binding site for Nedd4-2, an E3 ubiquitin protein ligase that targets ENaC for degradation. Mutations that delete or disrupt this motif cause accumulation of channels at the cell surface, resulting in Liddle\u2019s syndrome, an inherited form of hypertension. Nedd4-2 is a central convergence point for ENaC regulation by aldosterone and vasopressin; both induce phosphorylation of a common set of three Nedd4-2 residues, which blocks Nedd4-2 binding to ENaC. Thus, aldosterone and vasopressin regulate epithelial Na+ transport in part by altering ENaC trafficking to and from the cell surface.<\/jats:p>","DOI":"10.1210\/en.2005-0894","type":"journal-article","created":{"date-parts":[[2005,9,9]],"date-time":"2005-09-09T00:43:34Z","timestamp":1126226614000},"page":"5079-5085","source":"Crossref","is-referenced-by-count":204,"title":["Minireview: Regulation of Epithelial Na+ Channel Trafficking"],"prefix":"10.1210","volume":"146","author":[{"given":"Peter M.","family":"Snyder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612460354000_R1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1101\/sqb.2002.67.445","article-title":"Salt and blood pressure: new insight from human genetic studies.","volume":"67","author":"Lifton","year":"2002","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"2020071612460354000_R2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/361467a0","article-title":"Epithelial sodium channel related to proteins involved in neurodegeneration.","volume":"361","author":"Canessa","year":"1993","journal-title":"Nature"},{"key":"2020071612460354000_R3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0014-5793(93)81336-X","article-title":"Expression cloning of an epithelial amiloride-sensitive Na+ channel. 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function.","volume":"280","author":"Volk","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071612460354000_R41","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0896-6273(00)80708-4","article-title":"A new ER trafficking signal regulates the subunit stoichiometry of plasma membrane K(ATP) channels.","volume":"22","author":"Zerangue","year":"1999","journal-title":"Neuron"},{"key":"2020071612460354000_R42","doi-asserted-by":"crossref","first-page":"18111","DOI":"10.1074\/jbc.C400080200","article-title":"Epithelial sodium channels are activated by furin-dependent proteolysis.","volume":"279","author":"Hughey","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071612460354000_R43","doi-asserted-by":"crossref","first-page":"C190","DOI":"10.1152\/ajpcell.00342.2003","article-title":"Serine protease activation of near-silent epithelial Na+ channels","volume":"286","author":"Caldwell","year":"2004","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071612460354000_R44","doi-asserted-by":"crossref","first-page":"48491","DOI":"10.1074\/jbc.C400460200","article-title":"Distinct pools of epithelial sodium channels are expressed at the plasma membrane.","volume":"279","author":"Hughey","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071612460354000_R45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1085\/jgp.111.1.127","article-title":"Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes.","volume":"111","author":"Chraibi","year":"1998","journal-title":"J Gen Physiol"},{"key":"2020071612460354000_R46","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/39329","article-title":"An epithelial serine protease activates the amiloride-sensitive sodium channel.","volume":"389","author":"Vallet","year":"1997","journal-title":"Nature"},{"key":"2020071612460354000_R47","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1085\/jgp.20028598","article-title":"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.","volume":"120","author":"Vuagniaux","year":"2002","journal-title":"J Gen Physiol"},{"key":"2020071612460354000_R48","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1093\/hmg\/11.23.2829","article-title":"The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8\/10 activates the epithelial sodium channel (ENaC) in vitro.","volume":"11","author":"Guipponi","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2020071612460354000_R49","doi-asserted-by":"crossref","first-page":"L813","DOI":"10.1152\/ajplung.00435.2004","article-title":"Neutrophil elastase activates 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Chem"},{"key":"2020071612460354000_R56","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1085\/jgp.200409124","article-title":"Acute ENaC stimulation by cAMP in a kidney cell line is mediated by exocytic insertion from a recycling channel pool.","volume":"125","author":"Butterworth","year":"2005","journal-title":"J Gen Physiol"},{"key":"2020071612460354000_R57","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1073\/pnas.92.4.1013","article-title":"Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.","volume":"92","author":"Nielsen","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612460354000_R58","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/0092-8674(95)90212-0","article-title":"Mechanism by which Liddle\u2019s syndrome mutations increase activity of a human epithelial Na+ 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