The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate
- Mistry, Abinash C. Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA
- Wynne, Brandi M. Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA
- Yu, Ling The College of Resources and Environmental Science at Nanjing Agricultural University, Nanjing 210095, China
- Tomilin, Viktor Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Yue, Qiang Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Zhou, Yiqun Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Al-Khalili, Otor Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Mallick, Rickta Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA
- Cai, Hui Research Service, Atlanta Veteran's Administration Medical Center, Decatur, GA 30033, USA
- Alli, Abdel A. Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Ko, Benjamin Department of Medicine, University of Chicago, Chicago, IL 60637, USA
- Mattheyses, Alexa Department of Cell Biology, Emory University, Atlanta, GA 30322, USA
- Bao, Hui-Fang Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Pochynyuk, Oleh Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Theilig, Franziska Department of Medicine, University of Fribourg, Fribourg 1700, Switzerland
- Eaton, Douglas C. Department of Physiology, Emory University, Atlanta, GA 30322, USA
- Hoover, Robert S. Research Service, Atlanta Veteran's Administration Medical Center, Decatur, GA 30033, USA
- 2016-9-27
Published in:
- Biochemical Journal. - Portland Press Ltd.. - 2016, vol. 473, no. 19, p. 3237-3252
English
The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are coexpressed, the second part of the distal convoluted tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and coexpression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by blue native PAGE. Extensive coimmunoprecipitation experiments demonstrated a consistent interaction of NCC with α- and γ-ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence resonance energy transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting the function of ENaC. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1042/bcj20160312
- ISSN 0264-6021
- Persistent URL
- https://sonar.ch/global/documents/23522
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