Influence of proteolytic cleavage of ENaC’s γ subunit upon Na+ and K+ handling

Author:

Ray Evan C.1ORCID,Nickerson Andrew1ORCID,Sheng Shaohu1ORCID,Carrisoza-Gaytan Rolando2,Lam Tracey1,Marciszyn Allison1,Zhang Lei1,Jordahl Alexa1,Bi Chunming3,Winfrey Aaliyah1,Kou Zhaohui3,Gingras Sebastien3,Kirabo Annet45ORCID,Satlin Lisa M.2ORCID,Kleyman Thomas R.167ORCID

Affiliation:

1. Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

2. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York City, New York, United States

3. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

4. Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States

5. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States

6. Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

7. Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Abstract

The epithelial Na+ channel (ENaC) is activated in vitro by post-translational proteolysis. In vivo, low Na+ or high K+ diets enhance ENaC proteolysis, and proteolysis is hypothesized to contribute to channel activation in these settings. Using a mouse expressing ENaC with disruption of a key proteolytic cleavage site, this study demonstrates that impaired proteolytic activation of ENaC’s γ subunit has little impact upon channel open probability or the ability of mice to adapt to low Na+ or high K+ diets.

Funder

ASN Foundation for Kidney Research

HHS | NIH | NHLBI | Division of Intramural Research

HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases

HHS | NIH | National Center for Advancing Translational Sciences

Publisher

American Physiological Society

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