Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity

Tetsuhisa Otani, Thanh Phuong Nguyen, Shinsaku Tokuda, Kei Sugihara, Taichi Sugawara, Kyoko Furuse, Takashi Miura, Klaus Ebnet, Mikio Furuse

研究成果: Contribution to journalArticle査読

26 被引用数 (Scopus)

抄録

Tight junctions (TJs) establish the epithelial barrier and are thought to form a membrane fence to regulate epithelial polarity, although the roles of TJs in epithelial polarity remain controversial. Claudins constitute TJ strands in conjunction with the cytoplasmic scaffolds ZO-1 and ZO-2 and play pivotal roles in epithelial barrier formation. However, how claudins and other TJ membrane proteins cooperate to organize TJs remains unclear. Here, we systematically knocked out TJ components by genome editing and show that while ZO-1/ZO-2-deficient cells lacked TJ structures and epithelial barriers, claudin-deficient cells lacked TJ strands and an electrolyte permeability barrier but formed membrane appositions and a macromolecule permeability barrier. Moreover, epithelial polarity was disorganized in ZO-1/ZO-2-deficient cells, but not in claudin-deficient cells. Simultaneous deletion of claudins and a TJ membrane protein JAM-A resulted in a loss of membrane appositions and a macromolecule permeability barrier and in sporadic epithelial polarity defects. These results demonstrate that claudins and JAM-A coordinately regulate TJ formation and epithelial polarity.

本文言語英語
ページ(範囲)3372-3396
ページ数25
ジャーナルThe Journal of cell biology
218
10
DOI
出版ステータス出版済み - 10 7 2019

All Science Journal Classification (ASJC) codes

  • Cell Biology

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