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

TitleCLIC4 regulates apical exocytosis and renal tube luminogenesis through retromer- and actin-mediated endocytic trafficking.
Publication TypeJournal Article
Year of Publication2016
AuthorsChou S-Y, Hsu K-S, Otsu W, Hsu Y-C, Luo Y-C, Yeh C, Shehab SS, Chen J, Shieh V, He G-an, Marean MB, Felsen D, Ding A, Poppas DP, Chuang J-Z, Sung C-H
JournalNat Commun
Volume7
Pagination10412
Date Published2016 Jan 20
ISSN2041-1723
KeywordsActins, Animals, Chloride Channels, Dogs, Endosomes, Exocytosis, Immunoprecipitation, Madin Darby Canine Kidney Cells, Mice, Mice, Knockout, Mitochondrial Proteins, Protein Transport
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.

DOI10.1038/ncomms10412
Alternate JournalNat Commun
PubMed ID26786190
PubMed Central IDPMC4736046
Grant ListR01 EY011307 / EY / NEI NIH HHS / United States
R01 EY016805 / EY / NEI NIH HHS / United States
EY 016805 / EY / NEI NIH HHS / United States
NIH RO1 EY11307 / EY / NEI NIH HHS / United States