{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:51:18Z","timestamp":1778277078763,"version":"3.51.4"},"reference-count":68,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:p>Epithelial sodium channels (ENaCs) are composed of three structurally related subunits that form a tetrameric channel. The Xenopus laevis oocyte expression system was used to identify regions within the ENaC \u03b1-subunit that confer a dominant negative phenotype on functional expression of \u03b1\u03b2\u03b3-ENaC to define domains that have a role in subunit-subunit interactions. Coexpression of full-length mouse \u03b1\u03b2\u03b3-ENaC with either 1) the \u03b1-subunit first membrane-spanning domain and short downstream hydrophobic domain (\u03b1-M1H1); 2) \u03b1-M1H1 and its downstream hydrophilic extracellular loop (\u03b1-M1H1-ECL); 3) the membrane-spanning domain of a control type 2 transmembrane protein (glutamyl transpeptidase; \u03b3-GT) fused to the \u03b1-ECL (\u03b3-GT-\u03b1-ECL); 4) the extracellular domain of a control type 1 transmembrane protein (Tac) fused to the \u03b1-subunit second membrane-spanning domain and short upstream hydrophobic domain (Tac-\u03b1-H2M2); or 5) the \u03b1-subunit cytoplasmic COOH terminus (\u03b1-Ct) significantly reduced amiloride-sensitive Na<jats:sup>+<\/jats:sup>currents in X. laevis oocytes. Functional expression of Na<jats:sup>+<\/jats:sup>channels was not inhibited when full-length \u03b1\u03b2\u03b3-ENaC was coexpressed with either 1) the \u03b1-ECL lacking a signal-anchor sequence, 2) \u03b1-M1H1 and \u03b1-Ct expressed as a fusion protein, 3) full-length \u03b3-GT, or 4) full-length Tac. Furthermore, the expression of ROMK channels was not inhibited when full-length ROMK was coexpressed with either \u03b1-M1H1-ECL or \u03b1-Ct. Full-length FLAG-tagged \u03b1-, \u03b2-, or \u03b3-ENaC coimmunoprecipitated with myc-tagged \u03b1-M1H1-ECL, whereas wild-type \u03b3-GT did not. These data suggest that multiple sites within the \u03b1-subunit participate in subunit-subunit interactions that are required for proper assembly of the heterooligomeric ENaC complex.<\/jats:p>","DOI":"10.1152\/ajprenal.00095.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:39:30Z","timestamp":1425415170000},"page":"F600-F609","source":"Crossref","is-referenced-by-count":16,"title":["Multiple epithelial Na<sup>+<\/sup>channel domains participate in subunit assembly"],"prefix":"10.1152","volume":"285","author":[{"given":"James B.","family":"Bruns","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baofeng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon J.","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaohu","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca P.","family":"Hughey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas R.","family":"Kleyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4908"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.43.27295"},{"key":"REF3","doi-asserted-by":"crossref","unstructured":"Ahn YJ, Brooker DR, Kosari F, Harte BJ, Li J, Mackler SA, and Kleyman TR.Cloning and functional expression of the mouse epithelial sodium channel.Am J Physiol Renal Physiol277: F121\u2013F129, 1999.","DOI":"10.1152\/ajprenal.1999.277.1.F121"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.11.3.819"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00631.x"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-002-0945-8"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.267.6.C1682"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1038\/367463a0"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.46.32889"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-248"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.35.22693"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.1.C231"},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.20028559"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-001-0098-x"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.11.5796"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.2.344"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.5.2743"},{"key":"REF18","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(97)78808-8"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.51.36415"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.5.899"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1007\/s004249900119"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.1038\/ng0995-76"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110904200"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1016\/0019-2791(72)90096-1"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1999.276.3.G567"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"Inoue J, Iwaoka T, Tokunaga H, Takamune K, Naomi S, Araki M, Takahama K, Yamaguchi K, and Tomita K.A family with Liddle's syndrome caused by a new missense mutation in the beta subunit of the epithelial sodium channel.J Clin Endocrinol Metab83: 2210\u20132213, 1998.","DOI":"10.1210\/jcem.83.6.5030"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.34.21075"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004352200"},{"key":"REF29","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.118.6.679"},{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.4170"},{"key":"REF31","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.114.1.13"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00007.2002"},{"key":"REF33","unstructured":"Kleyman TR, Sheng S, Kosari F, and Kieber-Emmons T.Mechanism of action of amiloride: a molecular prospective.Semin Nephrol19: 524\u2013532, 1999."},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13469"},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77892-0"},{"key":"REF36","doi-asserted-by":"crossref","unstructured":"Langloh AL, Berdiev B, Ji HL, Keyser K, Stanton BA, and Benos DJ.Charged residues in the M2 region of \u03b1-hENaC play a role in channel conductance.Am J Physiol Cell Physiol278: C277\u2013C291, 2000.","DOI":"10.1152\/ajpcell.2000.278.2.C277"},{"key":"REF37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300149200"},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.2926"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.146.2.345"},{"key":"REF40","doi-asserted-by":"crossref","unstructured":"May A, Puoti A, Gaeggeler HP, Horisberger JD, and Rossier BC.Early effect of aldosterone on the rate of synthesis of the epithelial sodium channel alpha subunit in A6 renal cells.J Am Soc Nephrol8: 1813\u20131822, 1997.","DOI":"10.1681\/ASN.V8121813"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1042\/bj3360705"},{"key":"REF42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.28.16962"},{"key":"REF43","doi-asserted-by":"crossref","unstructured":"Renard S, Lingueglia E, Voilley N, Lazdunski M, and Barbry P.Biochemical analysis of the membrane topology of the amiloride-sensitive Na+channel.J Biol Chem269: 12981\u201312986, 1994.","DOI":"10.1016\/S0021-9258(18)99972-2"},{"key":"REF44","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.082101.143243"},{"key":"REF45","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.3.F391"},{"key":"REF46","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.109.1.15"},{"key":"REF47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8572"},{"key":"REF48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008117200"},{"key":"REF49","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108522200"},{"key":"REF50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209975200"},{"key":"REF51","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90250-X"},{"key":"REF52","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0458"},{"key":"REF53","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.116.6.781"},{"key":"REF54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.2.681"},{"key":"REF55","doi-asserted-by":"crossref","unstructured":"Snyder PM, McDonald FJ, Stokes JB, and Welsh MJ.Membrane topology of the amiloride-sensitive epithelial sodium channel.J Biol Chem269: 24379\u201324383, 1994.","DOI":"10.1016\/S0021-9258(19)51094-8"},{"key":"REF56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.40.28484"},{"key":"REF57","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00320.2001"},{"key":"REF58","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-248"},{"key":"REF59","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118606"},{"key":"REF60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.31.18904"},{"key":"REF61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5866"},{"key":"REF62","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(00)00217-7"},{"key":"REF63","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1999.277.3.F319"},{"key":"REF64","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)60602-0"},{"key":"REF65","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003822200"},{"key":"REF66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.16.10823"},{"key":"REF67","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2001.22072"},{"key":"REF68","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02030-X"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00095.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T09:38:10Z","timestamp":1651397890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00095.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["10.1152\/ajprenal.00095.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00095.2003","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}