PUBLICATION

Role of zebrafish ClC-K/barttin channels in apical kidney chloride reabsorption

Authors
Pérez-Rius, C., Castellanos, A., Gaitán-Peñas, H., Navarro, A., Artuch, R., Barrallo-Gimeno, A., Estévez, R.
ID
ZDB-PUB-190610-4
Date
2019
Source
The Journal of physiology   597(15): 3969-3983 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Chlorides/metabolism
  • HEK293 Cells
  • Humans
  • Kidney/metabolism*
  • Mutation
  • Protein Transport
  • Renal Reabsorption*
  • Zebrafish
PubMed
31177533 Full text @ J. Physiol.
Abstract
We have characterized the zebrafish clc-k and barttin proteins, demonstrating that they form a protein complex mediating chloride flux in a similar manner to their mammalian counterparts. As in mammals, in zebrafish, clc-k and barttin are basically expressed in the kidney. Contrary to what is found in mammals, in zebrafish both proteins show an apical localization in the kidney. We have generated the first knockout in zebrafish of a CLC protein. Lack of clc-k in zebrafish resulted in embryonic lethality, possibly caused by a reduction in total chloride content. As a consequence, there is an up-regulation other chloride channels and other regulatory mechanism such as renin or the uro-guanylin receptor in the kidney. barttin is mislocalized in vivo when clc-k is not present, indicating that there is a mutual dependence of the protein expression and localization between barttin and clc-k proteins.
ClC-K/barttin channels are very important for salt transport in the kidney. This function can be clearly seen as mutations in CLCNKB or BSND cause Bartter's syndrome type III and IV, respectively. Working with the freshwater teleost zebrafish, we characterized the genes homologous to the mammalian chloride channel ClC-K and its obligate subunit barttin and we obtained and studied clc-k knockout zebrafish. The zebrafish clc-k/barttin proteins are very similar to their mammalian counterparts, and both proteins are necessary to mediate chloride currents. Localization studies indicated that both proteins are exclusively expressed in the apical membranes of zebrafish kidney tubules. Knockout of clc-k resulted in embryonic lethality. These animals showed barttin mislocalization and a reduction in whole-body chloride concentration, as well as up-regulation of the expression of other chloride channels, renin and also an increase in the kidney expression of the uroguanylin receptor. Our results indicate that apical kidney chloride reabsorption through clc-k/barttin channels is crucial for chloride homeostasis in zebrafish as happens in humans. The zebrafish model could be used as a new in vivo system to study ClC-K function. This article is protected by copyright. All rights reserved.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes