Role of the ubiquitin system in regulating ion transport

Pflugers Arch. 2011 Jan;461(1):1-21. doi: 10.1007/s00424-010-0893-2. Epub 2010 Oct 23.


Ion channels and transporters play a critical role in ion and fluid homeostasis and thus in normal animal physiology and pathology. Tight regulation of these transmembrane proteins is therefore essential. In recent years, many studies have focused their attention on the role of the ubiquitin system in regulating ion channels and transporters, initialed by the discoveries of the role of this system in processing of Cystic Fibrosis Transmembrane Regulator (CFTR), and in regulating endocytosis of the epithelial Na(+) channel (ENaC) by the Nedd4 family of ubiquitin ligases (mainly Nedd4-2). In this review, we discuss the role of the ubiquitin system in ER Associated Degradation (ERAD) of ion channels, and in the regulation of endocytosis and lysosomal sorting of ion channels and transporters, focusing primarily in mammalian cells. We also briefly discuss the role of ubiquitin like molecules (such as SUMO) in such regulation, for which much less is known so far.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / physiology
  • Animals
  • Calcium Channels / physiology
  • Chloride Channels / physiology
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology
  • Endocytosis / physiology
  • Endoplasmic Reticulum / physiology*
  • Endosomal Sorting Complexes Required for Transport / physiology
  • Epithelial Sodium Channels / metabolism
  • Humans
  • Immediate-Early Proteins / physiology
  • Ion Transport / physiology*
  • Membrane Proteins / metabolism
  • Nedd4 Ubiquitin Protein Ligases
  • Potassium Channels, Voltage-Gated / physiology
  • Protein-Serine-Threonine Kinases / physiology
  • Small Ubiquitin-Related Modifier Proteins / physiology
  • Sodium Channels / physiology
  • Ubiquitin / physiology*
  • Ubiquitin-Protein Ligases / physiology
  • Ubiquitination / physiology*
  • Vasopressins / physiology


  • Calcium Channels
  • Chloride Channels
  • Endosomal Sorting Complexes Required for Transport
  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Membrane Proteins
  • Potassium Channels, Voltage-Gated
  • Small Ubiquitin-Related Modifier Proteins
  • Sodium Channels
  • Ubiquitin
  • Vasopressins
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Aldosterone
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Nedd4L protein, human
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase