HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 17, 13744-13749, April 27, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/17/13744    most recent M011273200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dinudom, A. Articles by Cook, D. I. Search for Related Content PubMed PubMed Citation Articles by Dinudom, A. Articles by Cook, D. I. Social Bookmarking                      What's this?

Roles of the C Termini of -, -, and -Subunits of Epithelial Na⁺ Channels (ENaC) in Regulating ENaC and Mediating Its Inhibition by Cytosolic Na^+*

Anuwat Dinudom, Kieran F. Harvey^§, Permsak Komwatana, Corina N. Jolliffe^§, John A. Young, Sharad Kumar^§¶, and David I. Cook^**

From the  Department of Physiology, University of Sydney, New South Wales 2006, Australia and the ^§ Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia

The amiloride-sensitive epithelial Na⁺ channels (ENaC) in the intralobular duct cells of mouse mandibular glands are inhibited by the ubiquitin-protein ligase, Nedd4, which is activated by increased intracellular Na⁺. In this study we have used whole-cell patch clamp methods in mouse mandibular duct cells to investigate the role of the C termini of the -, -, and -subunits of ENaC in mediating this inhibition. We found that peptides corresponding to the C termini of the - and -subunits, but not the -subunit, inhibited the activity of the Na⁺ channels. This mechanism did not involve Nedd4 and probably resulted from the exogenous C termini interfering competitively with the protein-protein interactions that keep the channels active. In the case of the C terminus of mouse -ENaC, the interacting motif included Ser⁶³¹, Asp⁶³², and Ser⁶³³. In the C terminus of mouse -ENaC, it included Ser⁶⁴⁰. Once these motifs were deleted, we were able to use the C termini of - and -ENaC to prevent Nedd4-mediated down-regulation of Na⁺ channel activity. The C terminus of the -subunit, on the contrary, did not prevent Nedd4-mediated inhibition of the Na⁺ channels. We conclude that mouse Nedd4 interacts with the - and -subunits of ENaC.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. Zhang, Q. Hou, M. Wang, A. Lin, L. Jarzylo, A. Navis, A. Raissi, F. Liu, and H.-Y. Man Na,K-ATPase Activity Regulates AMPA Receptor Turnover through Proteasome-Mediated Proteolysis J. Neurosci., April 8, 2009; 29(14): 4498 - 4511. [Abstract] [Full Text] [PDF]

				A. Anantharam, Y. Tian, and L. G. Palmer Open probability of the epithelial sodium channel is regulated by intracellular sodium J. Physiol., July 15, 2006; 574(2): 333 - 347. [Abstract] [Full Text] [PDF]

				A. Dinudom, A. B. Fotia, R. J. Lefkowitz, J. A. Young, S. Kumar, and D. I. Cook The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels PNAS, August 10, 2004; 101(32): 11886 - 11890. [Abstract] [Full Text] [PDF]

				L. M. Shearwin-Whyatt, D. L. Brown, F. G. Wylie, J. L. Stow, and S. Kumar N4WBP5A (Ndfip2), a Nedd4-interacting protein, localizes to multivesicular bodies and the Golgi, and has a potential role in protein trafficking J. Cell Sci., July 15, 2004; 117(16): 3679 - 3689. [Abstract] [Full Text] [PDF]

				M. D. Carattino, S. Sheng, and T. R. Kleyman Epithelial Na+ Channels Are Activated by Laminar Shear Stress J. Biol. Chem., February 6, 2004; 279(6): 4120 - 4126. [Abstract] [Full Text] [PDF]

				R. E. Booth, Q. Tong, J. Medina, P. M. Snyder, P. Patel, and J. D. Stockand A Region Directly Following the Second Transmembrane Domain in {gamma}ENaC Is Required for Normal Channel Gating J. Biol. Chem., October 17, 2003; 278(42): 41367 - 41379. [Abstract] [Full Text] [PDF]

				A. Becchetti, B. Malik, G. Yue, P. Duchatelle, O. Al-Khalili, T. R. Kleyman, and D. C. Eaton Phosphatase inhibitors increase the open probability of ENaC in A6 cells Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1030 - F1045. [Abstract] [Full Text] [PDF]

				E. Hendron, P. Patel, M. Hausenfluke, N. Gamper, M. S. Shapiro, R. E. Booth, and J. D. Stockand Identification of Cytoplasmic Domains within the Epithelial Na+ Channel Reactive at the Plasma Membrane J. Biol. Chem., September 6, 2002; 277(37): 34480 - 34488. [Abstract] [Full Text] [PDF]