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

doi:10.1038/ncomms10412

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 journal › Article › peer-review

37 Scopus citations

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 language	English (US)
Article number	10412
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10412
State	Published - Jan 20 2016
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms10412

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Chou, S. Y., Hsu, K. S., Otsu, W., Hsu, Y. C., Luo, Y. C., Yeh, C., Shehab, S. S., Chen, J., Shieh, V., He, G. A., Marean, M. B., Felsen, D., Ding, A., Poppas, D. P., Chuang, J. Z., & Sung, C. H. (2016). CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking. Nature communications, 7, Article 10412. https://doi.org/10.1038/ncomms10412

@article{c31a4539a67042d8a0061a89f5b56389,

title = "CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking",

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.",

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

note = "Funding Information: This work is supported by NIH RO1 EY11307, EY 016805, and Research To Prevent Blindness (to C.H.S.), National Science Council Postdoctoral Fellowship NSC 9729171564112, Taiwan (to S.Y.C.), and Frederick J and Theresa Dow Wallace fund of the New York Community Trust (D.P.). We are grateful to our colleagues for sharing reagents and Dr Scott Weed for discussion on cortactin biology.",

year = "2016",

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day = "20",

doi = "10.1038/ncomms10412",

language = "English (US)",

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T1 - CLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking

AU - Chou, Szu Yi

AU - Hsu, Kuo Shun

AU - Otsu, Wataru

AU - Hsu, Ya Chu

AU - Luo, Yun Cin

AU - Yeh, Celine

AU - Shehab, Syed S.

AU - Chen, Jie

AU - Shieh, Vincent

AU - He, Guo An

AU - Marean, Michael B.

AU - Felsen, Diane

AU - Ding, Aihao

AU - Poppas, Dix P.

AU - Chuang, Jen Zen

AU - Sung, Ching Hwa

N1 - Funding Information: This work is supported by NIH RO1 EY11307, EY 016805, and Research To Prevent Blindness (to C.H.S.), National Science Council Postdoctoral Fellowship NSC 9729171564112, Taiwan (to S.Y.C.), and Frederick J and Theresa Dow Wallace fund of the New York Community Trust (D.P.). We are grateful to our colleagues for sharing reagents and Dr Scott Weed for discussion on cortactin biology.

PY - 2016/1/20

Y1 - 2016/1/20

N2 - 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.

AB - 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.

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

Abstract

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