Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:


The structure of Na+-K+-Cl cotransporter 1

A recent study reports the first high-resolution, cryo-electron microscopy-based structure of zebrafish Na+-K+-Cl cotransporter 1 (NKCC1). This structure provides important insights into the determinants of ion translocation by NKCC1 and other cation-Cl cotransporters such as NKCC2. It could thus facilitate the design of drugs to target these transporters individually.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The structure of zebrafish NKCC1.


  1. Chew, T. A. et al. Structure and mechanism of the cation-chloride cotransporter NKCC1. Nature 572, 488–492 (2019).

    Article  CAS  Google Scholar 

  2. Geck, P. et al. Electrically silent cotransport on Na+, K+ and Cl- in Ehrlich cells. Biochim. Biophys. Acta 600, 432–447 (1980).

    Article  CAS  Google Scholar 

  3. Xu, J. C. et al. Molecular cloning and functional expression of the bumetanide-sensitive Na-K-Cl cotransporter. Proc. Natl Acad. Sci. USA 91, 2201–2205 (1994).

    Article  CAS  Google Scholar 

  4. Igarashi, P. et al. Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am. J. Physiol. 269, F405–F418 (1995).

    CAS  PubMed  Google Scholar 

  5. Monette, M. Y. & Forbush, B. Regulatory activation is accompanied by movement in the C terminus of the Na-K-Cl cotransporter (NKCC1). J. Biol. Chem. 287, 2210–2220 (2012).

    Article  CAS  Google Scholar 

  6. Simard, C. F. et al. Self-interacting domains in the C terminus of a cation-Cl- cotransporter described for the first time. J. Biol. Chem. 279, 40769–40777 (2004).

    Article  CAS  Google Scholar 

  7. Isenring, P. et al. Mutagenic mapping of the Na-K-Cl cotransporter for domains involved in ion transport and bumetanide binding. J. Gen. Physiol. 112, 549–558 (1998).

    Article  CAS  Google Scholar 

  8. Marcoux, A. A. et al. Regulation of Na+-K+-Cl- cotransporter type 2 by the with no lysine kinase-dependent signaling pathway. Am. J. Physiol. Cell Physiol. 317, C20–C30 (2019).

    Article  CAS  Google Scholar 

  9. Marcoux, A. A. et al. Endocytic recycling of Na+ -K+-Cl- cotransporter type 2: importance of exon 4. J. Physiol. (2019).

    Article  PubMed  Google Scholar 

  10. Gimenez, I., Isenring, P. & Forbush, B. Spatially distributed alternative splice variants of the renal Na-K-Cl cotransporter exhibit dramatically different affinities for the transported ions. J. Biol. Chem. 277, 8767–8770 (2002).

    Article  CAS  Google Scholar 

Download references


The authors’ work is funded by the Canadian Institutes of Health Research and the Kidney Foundation of Canada.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Paul Isenring.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garneau, A.P., Isenring, P. The structure of Na+-K+-Cl cotransporter 1. Nat Rev Nephrol 15, 732–734 (2019).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing