scholarly journals Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome

1999 ◽  
Vol 103 (5) ◽  
pp. 667-673 ◽  
Author(s):  
Hugues Abriel ◽  
Johannes Loffing ◽  
John F. Rebhun ◽  
J. Howard Pratt ◽  
Laurent Schild ◽  
...  
Keyword(s):  
Na Channel ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Epithelial Na Channel

scholarly journals WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome.

1996 ◽  
Vol 15 (10) ◽  
pp. 2371-2380 ◽  
Author(s):  
O. Staub ◽  
S. Dho ◽  
P. Henry ◽  
J. Correa ◽  
T. Ishikawa ◽  
...  
Keyword(s):  
Na Channel ◽  
Ww Domains ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Epithelial Na Channel

scholarly journals Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel

Cell ◽  
1995 ◽  
Vol 83 (6) ◽  
pp. 969-978 ◽  
Author(s):  
Peter M. Snyder ◽  
Margaret P. Price ◽  
Fiona J. McDonald ◽  
Christopher M. Adams ◽  
Kenneth A. Volk ◽  
...  
Keyword(s):  
Na Channel ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Epithelial Na Channel

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

2001 ◽  
Vol 60 (2) ◽  
pp. 466-471 ◽  
Author(s):  
Elena Kamynina ◽  
Christophe Debonneville ◽  
Robert P. Hirt ◽  
Olivier Staub
Keyword(s):  
Na Channel ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Epithelial Na Channel

scholarly journals Inhibition of the Epithelial Na+Channel by Interaction of Nedd4 with a PY Motif Deleted in Liddle’s Syndrome

1998 ◽  
Vol 273 (45) ◽  
pp. 30012-30017 ◽  
Author(s):  
Christopher C. Goulet ◽  
Kenneth A. Volk ◽  
Christopher M. Adams ◽  
Lawrence S. Prince ◽  
John B. Stokes ◽  
...  
Keyword(s):  
Na Channel ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Py Motif ◽  
Epithelial Na Channel

scholarly journals Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin

2003 ◽  
Vol 285 (3) ◽  
pp. F459-F471 ◽  
Author(s):  
Muriel Auberson ◽  
Nicole Hoffmann-Pochon ◽  
A. Vandewalle ◽  
Stephan Kellenberger ◽  
Laurent Schild
Keyword(s):  
Cell Surface ◽  
Collecting Duct ◽  
Short Circuit ◽  
Critical Role ◽  
Na Channel ◽  
Cortical Collecting Duct ◽  
Liddle’S Syndrome ◽  
Liddle's Syndrome ◽  
Py Motif ◽  
In Cells

Liddle's syndrome is a monogenic form of hypertension caused by mutations in the PY motif of the COOH terminus of β- and γ-epithelial Na+ channel (ENaC) subunits. These mutations lead to retention of active channels at the cell surface. Because of the critical role of this PY motif in the stability of ENaCs at the cell surface, we have investigated its contribution to the ENaC response to aldosterone and vasopressin. Mutants of the PY motif in β- and γ-ENaC subunits (β-Y618A, β-P616L, β-R564stop, and γ-K570stop) were stably expressed by retroviral gene transfer in a renal cortical collecting duct cell line (mpkCCDcl4), and transepithelial Na+ transport was assessed by measurements of the benzamil-sensitive short-circuit current ( Isc). Cells that express ENaC mutants of the PY motif showed a five- to sixfold higher basal Isc compared with control cells and responded to stimulation by aldosterone (10-6 M) or vasopressin (10-9 M) with a further increase in Isc. The rates of the initial increases in Isc after aldosterone or vasopressin stimulation were comparable in cells transduced with wild-type and mutant ENaCs, but reversal of the effects of aldosterone and vasopressin was slower in cells that expressed the ENaC mutants. The conserved sensitivity of ENaC mutants to stimulation by aldosterone and vasopressin together with the prolonged activity at the cell surface likely contribute to the increased Na+ absorption in the distal nephron of patients with Liddle's syndrome.

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