Role of zebrafish ClC-K/barttin channels in apical kidney chloride reabsorption
Pérez-Rius, Carla (Universitat de Barcelona)
Castellanos, Aida (Universitat de Barcelona)
Gaitan Peñas, Hector (Universitat de Barcelona)
Navarro, Almudena (Universitat de Barcelona)
Artuch, R. (Institut de Recerca Sant Joan de Déu)
Estévez, Raúl (Universitat de Barcelona)

Fecha:	2019
Descripción:	15 pàg.
Resumen:	Key points: 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 of other chloride channels and other regulatory mechanisms 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. Abstract: ClC-K/barttin channels are very important for salt transport in the kidney. This function can be clearly seen since mutations in CLCNKB or BSND cause Bartter's syndrome types 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 and renin, and 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 it is in humans. The zebrafish model could be used as a new in vivo system to study ClC-K function.
Ayudas:	Ministerio de Economía y Competitividad SAF2015-70377 Agencia Estatal de Investigación RTI2018-093493-B-I00 Generalitat de Catalunya 2014/SGR-01178
Derechos:	Aquest material està protegit per drets d'autor i/o drets afins. Podeu utilitzar aquest material en funció del que permet la legislació de drets d'autor i drets afins d'aplicació al vostre cas. Per a d'altres usos heu d'obtenir permís del(s) titular(s) de drets.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió acceptada per publicar
Publicado en:	The Journal of Physiology, Vol. 597, Num. 15 (2019) , p. 3969-3983, ISSN 1469-7793

DOI: 10.1113/JP278069
PMID: 31177533

Postprint 16 p, 653.4 KB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados