The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel - PubMed (original) (raw)
. 2000 Sep 8;275(36):27947-56.
doi: 10.1074/jbc.M002848200.
Affiliations
- PMID: 10821834
- DOI: 10.1074/jbc.M002848200
Free article
The cytosolic termini of the beta- and gamma-ENaC subunits are involved in the functional interactions between cystic fibrosis transmembrane conductance regulator and epithelial sodium channel
H L Ji et al. J Biol Chem. 2000.
Free article
Abstract
Epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR) are co-localized in the apical membrane of many epithelia. These channels are essential for electrolyte and water secretion and/or reabsorption. In cystic fibrosis airway epithelia, a hyperactivated epithelial Na(+) conductance operates in parallel with defective Cl(-) secretion. Several groups have shown that CFTR down-regulates ENaC activity, but the mechanisms and the regulation of CFTR by ENaC are unknown. To test the hypothesis that ENaC and CFTR regulate each other, and to identify the region(s) of ENaC involved in the interaction between CFTR and ENaC, rENaC and its mutants were co-expressed with CFTR in Xenopus oocytes. Whole cell macroscopic sodium currents revealed that wild type (wt) alphabetagamma-rENaC-induced Na(+) current was inhibited by co-expression of CFTR, and further inhibited when CFTR was activated with a cAMP-raising mixture (CKT). Conversely, alphabetagamma-rENaC stimulated CFTR-mediated Cl(-) currents up to approximately 6-fold. Deletion mutations in the intracellular tails of the three rENaC subunits suggested that the carboxyl terminus of the beta subunit was required both for the down-regulation of ENaC by activated CFTR and the up-regulation of CFTR by ENaC. However, both the carboxyl terminus of the beta subunit and the amino terminus of the gamma subunit were essential for the down-regulation of rENaC by unstimulated CFTR. Interestingly, down-regulation of rENaC by activated CFTR was Cl(-)-dependent, while stimulation of CFTR by rENaC was not dependent on either cytoplasmic Na(+) or a depolarized membrane potential. In summary, there appear to be at least two different sites in ENaC involved in the intermolecular interaction between CFTR and ENaC.
Similar articles
- Cystic fibrosis transmembrane conductance regulator differentially regulates human and mouse epithelial sodium channels in Xenopus oocytes.
Yan W, Samaha FF, Ramkumar M, Kleyman TR, Rubenstein RC. Yan W, et al. J Biol Chem. 2004 May 28;279(22):23183-92. doi: 10.1074/jbc.M402373200. Epub 2004 Mar 26. J Biol Chem. 2004. PMID: 15047694 - Wild type but not deltaF508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes.
Mall M, Hipper A, Greger R, Kunzelmann K. Mall M, et al. FEBS Lett. 1996 Feb 26;381(1-2):47-52. doi: 10.1016/0014-5793(96)00079-8. FEBS Lett. 1996. PMID: 8641437 - Control of epithelial Na+ conductance by the cystic fibrosis transmembrane conductance regulator.
Kunzelmann K, Schreiber R, Nitschke R, Mall M. Kunzelmann K, et al. Pflugers Arch. 2000 Jun;440(2):193-201. doi: 10.1007/s004240000255. Pflugers Arch. 2000. PMID: 10898518 Review. - ENaC is inhibited by an increase in the intracellular Cl(-) concentration mediated through activation of Cl(-) channels.
Kunzelmann K. Kunzelmann K. Pflugers Arch. 2003 Jan;445(4):504-12. doi: 10.1007/s00424-002-0958-y. Epub 2002 Nov 20. Pflugers Arch. 2003. PMID: 12548397 Review.
Cited by
- Epithelial Na + Channels Function as Extracellular Sensors.
Kashlan OB, Wang XP, Sheng S, Kleyman TR. Kashlan OB, et al. Compr Physiol. 2024 Mar 29;14(2):1-41. doi: 10.1002/cphy.c230015. Compr Physiol. 2024. PMID: 39109974 Review. - Association of cystic fibrosis transmembrane conductance regulator with epithelial sodium channel subunits carrying Liddle's syndrome mutations.
Rooj AK, Cormet-Boyaka E, Clark EB, Qadri YJ, Lee W, Boddu R, Agarwal A, Tambi R, Uddin M, Parpura V, Sorscher EJ, Fuller CM, Berdiev BK. Rooj AK, et al. Am J Physiol Lung Cell Mol Physiol. 2021 Aug 1;321(2):L308-L320. doi: 10.1152/ajplung.00298.2020. Epub 2021 May 26. Am J Physiol Lung Cell Mol Physiol. 2021. PMID: 34037494 Free PMC article. - Cystic Fibrosis Lung Disease Modifiers and Their Relevance in the New Era of Precision Medicine.
Sepahzad A, Morris-Rosendahl DJ, Davies JC. Sepahzad A, et al. Genes (Basel). 2021 Apr 13;12(4):562. doi: 10.3390/genes12040562. Genes (Basel). 2021. PMID: 33924524 Free PMC article. Review. - Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions.
Beswick E, Amich J, Gago S. Beswick E, et al. Pathogens. 2020 Aug 6;9(8):639. doi: 10.3390/pathogens9080639. Pathogens. 2020. PMID: 32781694 Free PMC article. Review. - Proliferative regulation of alveolar epithelial type 2 progenitor cells by human Scnn1d gene.
Zhao R, Ali G, Chang J, Komatsu S, Tsukasaki Y, Nie HG, Chang Y, Zhang M, Liu Y, Jain K, Jung BG, Samten B, Jiang D, Liang J, Ikebe M, Matthay MA, Ji HL. Zhao R, et al. Theranostics. 2019 Oct 18;9(26):8155-8170. doi: 10.7150/thno.37023. eCollection 2019. Theranostics. 2019. PMID: 31754387 Free PMC article.