Nedd4-2 and the regulation of epithelial sodium transport.

Abstract:

:Nedd4-2 is a ubiquitin ligase previously demonstrated to regulate endocytosis and lysosomal degradation of the epithelial Na(+) channel (ENaC) and other ion channels and transporters. Recent studies using Nedd4-2 knockout mice specifically in kidney or lung epithelia has revealed a critical role for this E3 ubiquitin ligase in regulating salt and fluid transport in these tissues/organs and in maintaining homeostasis of body blood pressure. Interestingly, the primary targets for Nedd4-2 may differ in these two organs: in the lung Nedd4-2 targets ENaC, and loss of Nedd4-2 leads to excessive ENaC function and to cystic fibrosis - like lung disease, whereas in the kidney, Nedd4-2 targets the Na(+)/Cl(-) cotransporter (NCC) in addition to targeting ENaC. In accord, loss of Nedd4-2 in the distal nephron leads to increased NCC abundance and function. The aldosterone-responsive kinase, Sgk1, appears to be involved in the regulation of NCC by Nedd4-2 in the kidney, similar to its regulation of ENaC. Collectively, these new findings underscore the physiological importance of Nedd4-2 in regulating epithelial salt and fluid transport and balance.

journal_name

Front Physiol

journal_title

Frontiers in physiology

authors

Rotin D,Staub O

doi

10.3389/fphys.2012.00212

subject

Has Abstract

pub_date

2012-06-21 00:00:00

pages

212

issn

1664-042X

journal_volume

3

pub_type

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