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Renal physiology

Aldosterone-dependent NCC activation

Nature Reviews Nephrology volume 11, page 567 (2015)Cite this article

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A new study has identified a mechanism linking aldosterone to activation of the NaCl cotransporter (NCC), which has important roles in renal sodium reabsorption and blood-pressure homeostasis. “Aldosterone is a potent NCC activator, but the mechanism by which it interfaces with the WNK kinase pathway to trigger NCC phosphorylation and activation had not been defined,” explains researcher Arohan Subramanya.

When analysing the sequence of WNK1 kinase, Subramanya and colleagues noticed binding sites for the ubiquitin ligase NEDD4-2 in an proline-rich region that undergoes alternative splicing. They found that WNK1 isoforms containing these binding sites were highly expressed in human distal nephrons and were targeted for proteasomal degradation by NEDD4-2. “As NEDD4-2 can be blocked by the aldosterone-induced kinase SGK1, this finding suggested a mechanism by which aldosterone could increase WNK1 levels, resulting in increased WNK signalling and phosphorylation of NCC,” says Subramanya.

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References

  1. Roy, A. et al. Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action. J. Clin. Invest. 10.1172/JCI75245

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Authors
  1. Ellen F. Carney
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Carney, E. Aldosterone-dependent NCC activation. Nat Rev Nephrol 11, 567 (2015). https://doi.org/10.1038/nrneph.2015.145

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