Impaired acidification in early endosomes of ClC-5 deficient proximal tubule

Mariko Hara-Chikuma, Yinghong Wang, Sandra E. Guggino, William B. Guggino, A. S. Verkman

研究成果: Article査読

102 被引用数 (Scopus)


ClC-5 chloride channel deficiency causes proteinuria, hypercalciuria, and nephrolithiasis (Dent's disease). Impaired endosomal acidification in proximal tubule caused by reduced chloride conductance is a proposed mechanism; however, functional analysis of ClC-5 in oocytes predicts low ClC-5 chloride conductance in endosomes because of their acid interior pH and positive potential. Here, endosomal pH and chloride concentration were measured in proximal tubule cell cultures from wildtype vs. ClC-5 deficient mice using fluorescent sensors coupled to transferrin (early/recycling endosomes) or α2- macroglobulin (late endosomes). Initial pH in transferrin-labeled endosomes was ∼7.2, decreasing at 15 min to 6.0 vs. 6.5 in wildtype vs. ClC-5 deficient cells, respectively; corresponding endosomal chloride concentration increased from ∼16 mM to 47 vs. 36 mM. In contrast, acidification and chloride accumulation were not impaired in late endosomes or Golgi. Our results provide direct evidence for ClC-5 involvement in acidification of early endosomes in proximal tubule by a chloride shunt mechanism.

ジャーナルBiochemical and Biophysical Research Communications
出版ステータスPublished - 2005 4 15

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


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