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The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate.

  • Mistry AC Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA.
  • Wynne BM Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA.
  • Yu L Department of Physiology, Emory University, Atlanta, GA 30322, USA The College of Resources and Environmental Science at Nanjing Agricultural University, Nanjing 210095, China.
  • Tomilin V Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Yue Q Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Zhou Y Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Al-Khalili O Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Mallick R Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA.
  • Cai H Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA Department of Physiology, Emory University, Atlanta, GA 30322, USA Research Service, Atlanta Veteran's Administration Medical Center, Decatur, GA 30033, USA.
  • Alli AA Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Ko B Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
  • Mattheyses A Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
  • Bao HF Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Pochynyuk O Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
  • Theilig F Department of Medicine, University of Fribourg, Fribourg 1700, Switzerland.
  • Eaton DC Department of Physiology, Emory University, Atlanta, GA 30322, USA.
  • Hoover RS Division of Nephrology, Department of Medicine, Emory University, 615 Michael St, rm. 601, Atlanta, GA 30322, USA Department of Physiology, Emory University, Atlanta, GA 30322, USA Research Service, Atlanta Veteran's Administration Medical Center, Decatur, GA 30033, USA.
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  • 2016-07-17
Published in:
  • The Biochemical journal. - 2016
ion channels
protein–protein interactions
sodium channel
sodium chloride cotransporter
transport
Animals
Cell Line
Epithelial Sodium Channels
Fluorescence Resonance Energy Transfer
Kidney Cortex
Mice
Microscopy, Confocal
Protein Binding
Sodium Chloride Symporters
Two-Hybrid System Techniques
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.
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  • English
Open access status
green
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https://sonar.ch/global/documents/242146
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