WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway

Bo Zhou, Jieqiu Zhuang, Dingying Gu, Hua Wang, Liudmila Cebotaru, William B Guggino, Hui Cai

Research output: Contribution to journalArticle

Abstract

WNK kinase is a serine/threonine kinase that plays an important role in electrolyte homeostasis. WNK4 significantly inhibits the surface expression of the sodium chloride co-transporter (NCC) by enhancing the degradation of NCC through a lysosomal pathway, but the mechanisms underlying this trafficking are unknown. Here, we investigated the effect of the lysosomal targeting receptor sortilin on NCC expression and degradation. In Cos-7 cells, we observed that the presence of WNK4 reduced the steady-state amount of NCC by approximately half. Co-transfection with truncated sortilin (a dominant negative mutant) prevented this WNK4-induced reduction in NCC. NCC immunoprecipitated with both wild-type sortilin and, to a lesser extent, truncated sortilin. Immunostaining revealed that WNK4 increased the co-localization of NCC with the lysosomal marker cathepsin D, and NCC co-localized with wild-type sortilin, truncated sortilin, and WNK4 in the perinuclear region. These findings suggest that WNK4 promotes NCC targeting to the lysosome for degradation via a mechanism involving sortilin.

Original languageEnglish (US)
Pages (from-to)82-92
Number of pages11
JournalJournal of the American Society of Nephrology
Volume21
Issue number1
DOIs
StatePublished - Jan 2010

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Sodium Chloride Symporters
Symporters
Cathepsin D
Protein-Serine-Threonine Kinases
Lysosomes
sortilin
Electrolytes
Transfection
Homeostasis
Phosphotransferases

ASJC Scopus subject areas

  • Nephrology

Cite this

WNK4 enhances the degradation of NCC through a sortilin-mediated lysosomal pathway. / Zhou, Bo; Zhuang, Jieqiu; Gu, Dingying; Wang, Hua; Cebotaru, Liudmila; Guggino, William B; Cai, Hui.

In: Journal of the American Society of Nephrology, Vol. 21, No. 1, 01.2010, p. 82-92.

Research output: Contribution to journalArticle

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