NEDD4-2 (NEDD4L): the ubiquitin ligase for multiple membrane proteins

Gene. 2015 Feb 15;557(1):1-10. doi: 10.1016/j.gene.2014.11.051. Epub 2014 Nov 26.

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Epithelial Sodium Channels / metabolism*
  • Humans
  • Hypertension / physiopathology
  • KCNQ Potassium Channels / metabolism*
  • Mice
  • Nedd4 Ubiquitin Protein Ligases
  • Neoplasms / pathology
  • Protein Binding
  • Protein Transport
  • Pulmonary Surfactant-Associated Protein C / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Voltage-Gated Sodium Channels / metabolism*

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Epithelial Sodium Channels
  • KCNQ Potassium Channels
  • Pulmonary Surfactant-Associated Protein C
  • Receptors, Transforming Growth Factor beta
  • Voltage-Gated Sodium Channels
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Nedd4L protein, human
  • Nedd4l protein, mouse
  • Ubiquitin-Protein Ligases