Abstract
NEDD4-2 (also known as NEDD4L, neural precursor cell expressed developmentally down-regulated 4-like) is a ubiquitin protein ligase of the Nedd4 family which is known to bind and regulate a number of membrane proteins to aid in their internalization and turnover. Several of the NEDD4-2 substrates include ion channels, such as the epithelial and voltage-gated sodium channels. Given the critical function of NEDD4-2 in regulating membrane proteins, this ligase is essential for the maintenance of cellular homeostasis. In this article we review the biology and function of this important ubiquitin-protein ligase and discuss its pathophysiological significance.
Keywords:
Epithelial sodium channel (ENaC); Hypertension; NEDD4 family; Ubiquitin; Ubiquitin protein ligases; Voltage-gated sodium channels (Na(v)s).
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Blood Pressure / physiology
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Epithelial Sodium Channels / metabolism*
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Humans
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Hypertension / physiopathology
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KCNQ Potassium Channels / metabolism*
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Mice
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Nedd4 Ubiquitin Protein Ligases
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Neoplasms / pathology
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Protein Binding
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Protein Transport
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Pulmonary Surfactant-Associated Protein C / metabolism*
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Receptors, Transforming Growth Factor beta / metabolism
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Ubiquitin-Protein Ligases / metabolism*
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Ubiquitination
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Voltage-Gated Sodium Channels / metabolism*
Substances
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Endosomal Sorting Complexes Required for Transport
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Epithelial Sodium Channels
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KCNQ Potassium Channels
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Pulmonary Surfactant-Associated Protein C
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Receptors, Transforming Growth Factor beta
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Voltage-Gated Sodium Channels
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Nedd4 Ubiquitin Protein Ligases
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Nedd4 protein, human
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Nedd4L protein, human
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Nedd4l protein, mouse
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Ubiquitin-Protein Ligases