The WNK/SPAK and IRBIT/PP1 Pathways in Epithelial Fluid and Electrolyte Transport

Seonghee Park, Jeong Hee Hong, Ehud Ohana, Shmuel Muallem


Fluid and electrolyte homeostasis is a fundamental physiological function required for survival and is associated with a plethora of diseases when aberrant. Systemic fluid and electrolyte composition is regulated by the kidney, and all secretory epithelia generate biological fluids with defined electrolyte composition by vectorial transport of ions and the obligatory water. A major regulatory pathway that immerged in the last several years is regulation of ion transporters by the WNK/SPAK kinases and IRBIT/PP1 pathways. The IRBIT/PP1 pathway functions to reverse the effects of the WNK/SPAK kinases pathway, as was demonstrated for NBCe1-B and CFTR. Since many transporters involved in fluid and electrolyte homeostasis are affected by PP1 and/or calcineurin, it is possible that WNK/SPAK and IRBIT/PP1 form a common regulatory pathway to tune the activity of fluid and electrolyte transport in response to physiological demands.


  • The work in the authors' laboratory was funded by Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research Grant Z1A-DE-000735, and by the National Research Foundation of Korea Grant NRF-2009-352-E00046 funded by the Korean Government.

  • No conflicts of interest, financial or otherwise, are declared by the author(s).

View Full Text