Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel

Author(s)

Abd El-Aziz, T. M., Soares, A. G., Mironova, E., Boiko, N., Kaur, A., Archer, C. R., Stockand, J. D., & Berman, J. M.

Title

Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel

Date

2021

Publisher

Springer Science and Business Media LLC

Subject

Physiology
Cardiovascular biology
Kidney
Neurophysiology
Membrane trafficking
Ion channels
Sodium channels
Kinases
Cellular neuroscience

Language

English

Abstract

Activity of the Epithelial Na+ Channel (ENaC) in the distal nephron fine-tunes renal sodium excretion. Appropriate sodium excretion is a key factor in the regulation of blood pressure. Consequently, abnormalities in ENaC function can cause hypertension. Casein Kinase II (CKII) phosphorylates ENaC. The CKII phosphorylation site in ENaC resides within a canonical “anchor” ankyrin binding motif. CKII-dependent phosphorylation of ENaC is necessary and sufficient to increase channel activity and is thought to influence channel trafficking in a manner that increases activity. We test here the hypothesis that phosphorylation of ENaC by CKII within an anchor motif is necessary for ankyrin-3 (Ank-3) regulation of the channel, which is required for normal channel locale and function, and the proper regulation of renal sodium excretion. This was addressed using a fluorescence imaging strategy combining total internal reflection fluorescence (TIRF) microscopy with fluorescence recovery after photobleaching (FRAP) to quantify ENaC expression in the plasma membrane in living cells; and electrophysiology to quantify ENaC activity in split-open collecting ducts from principal cell-specific Ank-3 knockout mice. Sodium excretion studies also were performed in parallel in this knockout mouse. In addition, we substituted a key serine residue in the consensus CKII site in β-ENaC with alanine to abrogate phosphorylation and disrupt the anchor motif. Findings show that disrupting CKII signaling decreases ENaC activity by decreasing expression in the plasma membrane. In the principal cell-specific Ank-3 KO mouse, ENaC activity and sodium excretion were significantly decreased and increased, respectively. These results are consistent with CKII phosphorylation of ENaC functioning as a “switch” that favors Ank-3 binding to increase channel activity.

Source

Scientific Reports, Volume 11, Issue 1, July 2021, Article 14600

Rights

Copyright © The Author(s) 2021
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Format

PDF

Type

Text

Bibliographic Citation

Abd El-Aziz, T. M., Soares, A. G., Mironova, E., Boiko, N., Kaur, A., Archer, C. R., Stockand, J. D., & Berman, J. M. (2021). Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel. In Scientific Reports (Vol. 11, Issue 1). Springer Science and Business Media LLC. https://doi.org/10.1038/s41598-021-94118-3

Files

Berman_Jonathan - Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel.pdf

Citation

Abd El-Aziz, T. M., Soares, A. G., Mironova, E., Boiko, N., Kaur, A., Archer, C. R., Stockand, J. D., & Berman, J. M.,

Mechanisms and consequences of casein kinase II and ankyrin-3 regulation of the epithelial Na+ channel

. Scientific Reports, Volume 11, Issue 1, July 2021, Article 14600, New York Tech Institutional Repository, accessed April 20, 2024, https://repository.nyitlibrary.org/items/show/3703

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