CK2 Phosphorylation of ENaC Directs Ankyrin‐3 Activity

Abstract

The Epithelial Na+ Channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine‐tuning of electrolyte and water excretion and consequently, blood pressure. We recently showed that phosphorylation of ENaC by CK2 in a putative ANK3 binding domain regulates ENaC activity. Therefore we tested the necessity and sufficiency of ANK3 for normal ENaC function. We produced tissue specific ANK3 knockout mice in the aldosterone sensitive distal nephron. Knockout was verified by immunohistochemistry. Split open tubule recordings from these mice showed significantly decreased baseline ENaC activity. The mice displayed a insensitivity to the specific CK2 inhibitor TBB, a casein‐kinase II inhibitor compared to control. Together these results suggest that ANK3 modulates ENaC activity by interacting with CK2 phosphorylation sites in Beta and Gamma ENaC. In future work we will examine the mechanism by which this interaction modifies ENaC activity.Support or Funding InformationThis research was supported by American Heart Association Grants 15GRNT‐22930030 and 17GR‐NT‐3292002 (to J. D. Stockand) and 17POST33660468 (to J. M. Berman) and by National Institutes of Health Grants T32‐HL‐00744536A1 (to J. D. Stockand and J. M. Berman), K12GM111726 (to J. M. Berman), and F32‐DK‐104572 (to E. Mironova).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.