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Liddle's syndrome: a novel mouse Nedd4 isoform regulates the activity of the epithelial Na+ channel

Lookup NU author(s): Professor Robert Hirt

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Abstract

The epithelial Na(+) channel (ENaC), which plays an essential role in renal Na(+) handling, is composed of three subunits (alpha beta gamma), each containing a conserved PY motif at the C terminus. In Liddle's syndrome, an inherited form of salt-sensitive hypertension, the PY motifs of either beta or gamma ENaC are deleted or modified. We have recently shown that a ubiquitin-protein ligase Nedd4 binds via its WW domains to these PY motifs on ENaC, that ENaC is regulated by ubiquitination, and that Xenopus laevis Nedd4 (xNedd4) controls the cell surface pool of ENaC when coexpressed in Xenopus oocytes. Interestingly, Na(+) transporting cells, derived from mouse cortical collecting duct, express two different Nedd4 isoforms, which we have termed mNedd4-1 and mNedd4-2. Only mNedd4-2, which is orthologous to xNedd4, but not mNedd4-1, is able to regulate ENaC activity, and this property correlates with the capability to bind to the ENaC complex. Hence, Nedd4-2 may be encoded by a novel susceptibility gene for arterial hypertension.


Publication metadata

Author(s): Hirt RP; Kamynina E; Debonneville C; Staub O

Publication type: Article

Publication status: Published

Journal: Kidney International

Year: 2001

Volume: 60

Issue: 2

Pages: 466-471

ISSN (print): 0085-2538

ISSN (electronic): 1523-1755

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1046/j.1523-1755.2001.060002466.x

DOI: 10.1046/j.1523-1755.2001.060002466.x


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