WNK4 phosphorylates ser(206) of claudin-7 and promotes paracellular Cl(-) permeability

FEBS Lett. 2007 Aug 7;581(20):3887-91. doi: 10.1016/j.febslet.2007.07.014. Epub 2007 Jul 16.

Abstract

Mutations in WNK4 have been linked to hypertension in PHAII. Paracellular ion transport has been reported to be involved in this disease process; however, the specific molecular target has not been identified. In this study, we found that TJ protein claudin-7 and WNK4 were partially co-localized in renal tubules of rat kidney and co-immunoprecipitated in kidney epithelial cells. The wild-type and PHAII-causing mutant, but not the kinase-dead mutant, phosphorylated claudin-7. We have identified ser(206) in the COOH-terminus of claudin-7 as a putative phosphorylation site for WNK4. More importantly, disease-causing mutant enhanced claudin-7 phosphorylation and significantly increased paracellular permeability to Cl(-).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / metabolism
  • Amino Acid Substitution
  • Animals
  • Cell Membrane Permeability / physiology*
  • Chlorides / metabolism*
  • Epithelium / metabolism
  • Kidney / cytology
  • Kidney Tubules / metabolism
  • LLC-PK1 Cells
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Serine / metabolism*
  • Swine
  • Tight Junctions / physiology

Substances

  • Chlorides
  • Membrane Proteins
  • Serine
  • Wnk4 protein, rat
  • Protein-Serine-Threonine Kinases
  • Alanine