Differential N termini in epithelial Na+ channel δ-subunit isoforms modulate channel trafficking to the membrane - PubMed (original) (raw)
. 2012 Mar 15;302(6):C868-79.
doi: 10.1152/ajpcell.00255.2011. Epub 2011 Dec 7.
Affiliations
- PMID: 22159085
- DOI: 10.1152/ajpcell.00255.2011
Free article
Differential N termini in epithelial Na+ channel δ-subunit isoforms modulate channel trafficking to the membrane
Diana Wesch et al. Am J Physiol Cell Physiol. 2012.
Free article
Abstract
The epithelial Na(+) channel (ENaC) is a heteromultimeric ion channel that plays a key role in Na(+) reabsorption across tight epithelia. The canonical ENaC is formed by three analogous subunits, α, β, and γ. A fourth ENaC subunit, named δ, is expressed in the nervous system of primates, where its role is unknown. The human δ-ENaC gene generates at least two splice isoforms, δ(1) and δ(2) , differing in the N-terminal sequence. Neurons in diverse areas of the human and monkey brain differentially express either δ(1) or δ(2) , with few cells coexpressing both isoforms, which suggests that they may play specific physiological roles. Here we show that heterologous expression of δ(1) in Xenopus oocytes and HEK293 cells produces higher current levels than δ(2) . Patch-clamp experiments showed no differences in single channel current magnitude and open probability between isoforms. Steady-state plasma membrane abundance accounts for the dissimilarity in macroscopic current levels. Differential trafficking between isoforms is independent of β- and γ-subunits, PY-motif-mediated endocytosis, or the presence of additional lysine residues in δ(2)-N terminus. Analysis of δ(2)-N terminus identified two sequences that independently reduce channel abundance in the plasma membrane. The δ(1) higher abundance is consistent with an increased insertion rate into the membrane, since endocytosis rates of both isoforms are indistinguishable. Finally, we conclude that δ-ENaC undergoes dynamin-independent endocytosis as opposed to αβγ-channels.
Similar articles
- The neuronal-specific SGK1.1 kinase regulates {delta}-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling.
Wesch D, Miranda P, Afonso-Oramas D, Althaus M, Castro-Hernández J, Dominguez J, Morty RE, Clauss W, González-Hernández T, Alvarez de la Rosa D, Giraldez T. Wesch D, et al. Am J Physiol Cell Physiol. 2010 Oct;299(4):C779-90. doi: 10.1152/ajpcell.00184.2010. Epub 2010 Jul 14. Am J Physiol Cell Physiol. 2010. PMID: 20631247 - Incorporation of the δ-subunit into the epithelial sodium channel (ENaC) generates protease-resistant ENaCs in Xenopus laevis.
Wichmann L, Vowinkel KS, Perniss A, Manzini I, Althaus M. Wichmann L, et al. J Biol Chem. 2018 May 4;293(18):6647-6658. doi: 10.1074/jbc.RA118.002543. Epub 2018 Mar 25. J Biol Chem. 2018. PMID: 29576549 Free PMC article. - Cloning and functional expression of a new epithelial sodium channel delta subunit isoform differentially expressed in neurons of the human and monkey telencephalon.
Giraldez T, Afonso-Oramas D, Cruz-Muros I, Garcia-Marin V, Pagel P, González-Hernández T, Alvarez de la Rosa D. Giraldez T, et al. J Neurochem. 2007 Aug;102(4):1304-15. doi: 10.1111/j.1471-4159.2007.04622.x. Epub 2007 May 1. J Neurochem. 2007. PMID: 17472699 - ENaC in the brain--future perspectives and pharmacological implications.
Giraldez T, Domínguez J, Alvarez de la Rosa D. Giraldez T, et al. Curr Mol Pharmacol. 2013 Mar;6(1):44-9. doi: 10.2174/1874467211306010006. Curr Mol Pharmacol. 2013. PMID: 23547934 Review. - ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters.
Hanukoglu I. Hanukoglu I. FEBS J. 2017 Feb;284(4):525-545. doi: 10.1111/febs.13840. Epub 2016 Sep 15. FEBS J. 2017. PMID: 27580245 Review.
Cited by
- The neuronal serum- and glucocorticoid-regulated kinase 1.1 reduces neuronal excitability and protects against seizures through upregulation of the M-current.
Miranda P, Cadaveira-Mosquera A, González-Montelongo R, Villarroel A, González-Hernández T, Lamas JA, Alvarez de la Rosa D, Giraldez T. Miranda P, et al. J Neurosci. 2013 Feb 6;33(6):2684-96. doi: 10.1523/JNEUROSCI.3442-12.2013. J Neurosci. 2013. PMID: 23392695 Free PMC article. - Controlling epithelial sodium channels with light using photoswitchable amilorides.
Schönberger M, Althaus M, Fronius M, Clauss W, Trauner D. Schönberger M, et al. Nat Chem. 2014 Aug;6(8):712-9. doi: 10.1038/nchem.2004. Epub 2014 Jul 20. Nat Chem. 2014. PMID: 25054942 - Structural insights into subunit-dependent functional regulation in epithelial sodium channels.
Houser A, Baconguis I. Houser A, et al. Structure. 2025 Feb 6;33(2):349-362.e4. doi: 10.1016/j.str.2024.11.013. Epub 2024 Dec 11. Structure. 2025. PMID: 39667931 - Two Functional Epithelial Sodium Channel Isoforms Are Present in Rodents despite Pronounced Evolutionary Pseudogenization and Exon Fusion.
Gettings SM, Maxeiner S, Tzika M, Cobain MRD, Ruf I, Benseler F, Brose N, Krasteva-Christ G, Vande Velde G, Schönberger M, Althaus M. Gettings SM, et al. Mol Biol Evol. 2021 Dec 9;38(12):5704-5725. doi: 10.1093/molbev/msab271. Mol Biol Evol. 2021. PMID: 34491346 Free PMC article. - 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.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources