CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking

Szu Yi Chou, Kuo Shun Hsu, Wataru Otsu, Ya Chu Hsu, Yun Cin Luo, Celine Yeh, Syed S. Shehab, Jie Chen, Vincent Shieh, Guo An He, Michael B. Marean, Diane Felsen, Aihao Ding, Dix P. Poppas, Jen Zen Chuang, Ching Hwa Sung

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes.

Original languageEnglish
Article number10412
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Jan 20 2016
Externally publishedYes

Fingerprint

Chloride Channels
Exocytosis
Actins
Chlorides
chlorides
tubes
Kidney
Endosomes
lumens
delivery
biological evolution
phenotype
canals
Microvilli
Carrier transport
Morphogenesis
embryos
kidneys
Canals
mutations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking. / Chou, Szu Yi; Hsu, Kuo Shun; Otsu, Wataru; Hsu, Ya Chu; Luo, Yun Cin; Yeh, Celine; Shehab, Syed S.; Chen, Jie; Shieh, Vincent; He, Guo An; Marean, Michael B.; Felsen, Diane; Ding, Aihao; Poppas, Dix P.; Chuang, Jen Zen; Sung, Ching Hwa.

In: Nature Communications, Vol. 7, 10412, 20.01.2016.

Research output: Contribution to journalArticle

Chou, SY, Hsu, KS, Otsu, W, Hsu, YC, Luo, YC, Yeh, C, Shehab, SS, Chen, J, Shieh, V, He, GA, Marean, MB, Felsen, D, Ding, A, Poppas, DP, Chuang, JZ & Sung, CH 2016, 'CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking', Nature Communications, vol. 7, 10412. https://doi.org/10.1038/ncomms10412
Chou, Szu Yi ; Hsu, Kuo Shun ; Otsu, Wataru ; Hsu, Ya Chu ; Luo, Yun Cin ; Yeh, Celine ; Shehab, Syed S. ; Chen, Jie ; Shieh, Vincent ; He, Guo An ; Marean, Michael B. ; Felsen, Diane ; Ding, Aihao ; Poppas, Dix P. ; Chuang, Jen Zen ; Sung, Ching Hwa. / CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking. In: Nature Communications. 2016 ; Vol. 7.
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