Epithelial Na+ Channel: Reciprocal Control by COMMD10 and Nedd4-2

Frontiers in Physiology
Adam W WareFiona J McDonald

Abstract

Optimal function of the epithelial sodium channel (ENaC) in the distal nephron is key to the kidney's long-term control of salt homeostasis and blood pressure. Multiple pathways alter ENaC cell surface populations, including correct processing and trafficking in the secretory pathway to the cell surface, and retrieval from the cell surface through ubiquitination by the ubiquitin ligase Nedd4-2, clathrin-mediated endocytosis, and sorting in the endosomal system. Members of the Copper Metabolism Murr1 Domain containing (COMMD) family of 10 proteins are known to interact with ENaC. COMMD1, 3 and 9 have been shown to down-regulate ENaC, most likely through Nedd4-2, however, the other COMMD family members remain uncharacterized. To investigate the effects of the COMMD10 protein on ENaC trafficking and function, the interaction of ENaC and COMMD10 was confirmed. Stable COMMD10 knockdown in Fischer rat thyroid epithelia decreased ENaC current and this decreased current was associated with increased Nedd4-2 protein, a known negative regulator of ENaC. However, inhibition of Nedd4-2's ubiquitination of ENaC was only able to partially rescue the observed reduction in current. Stable COMMD10 knockdown results in defects both in endocytosi...Continue Reading

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Citations

Aug 1, 2019·American Journal of Physiology. Renal Physiology·Kubra M TunaAbdel A Alli
Oct 28, 2019·American Journal of Physiology. Renal Physiology·Adam W WareFiona J McDonald
Oct 6, 2020·American Journal of Physiology. Renal Physiology·Tanya T CheungFiona J McDonald
Dec 3, 2020·Disease Models & Mechanisms·Amika SinglaEzra Burstein
Jan 23, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Ralf Weiskirchen, Louis C Penning

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Methods Mentioned

BETA
ubiquitination
Transfection
transfect
pulldowns
protein assay
Assay
confocal microscopy
X-ray
pulldown

Software Mentioned

JACoP
Acquire and Analyze
ImageJ
Graph Pad Prism

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