Role of the ubiquitin system in regulating ion transport.
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.
Program in Cell Biology, The Hospital for Sick Children and Biochemistry Department, University of Toronto, Toronto, Canada. drotin@sickkids.ca
Daniela
D
Rotin
Olivier
O
Staub
D000450:Aldosterone / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000502:physiology; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D017136:Ion Transport / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D000075702:Nedd4 Ubiquitin Protein Ligases; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D025801:Ubiquitin / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D054875:Ubiquitination / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D015220:Calcium Channels; D018118:Chloride Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D024642:Potassium Channels, Voltage-Gated; D017346:Protein Serine-Threonine Kinases; D025841:Small Ubiquitin-Related Modifier Proteins; D015222:Sodium Channels; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D014667:Vasopressins; D000099184:Serum-Glucocorticoid Regulated Kinases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human