TY - JOUR
T1 - Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity
AU - Otani, Tetsuhisa
AU - Nguyen, Thanh Phuong
AU - Tokuda, Shinsaku
AU - Sugihara, Kei
AU - Sugawara, Taichi
AU - Furuse, Kyoko
AU - Miura, Takashi
AU - Ebnet, Klaus
AU - Furuse, Mikio
N1 - Funding Information:
This work was supported by a Japan Society for the Promotion of Science Grant-in-Aid for Challenging Exploratory Research (16K15226, M. Furuse), Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (B) (26291043 and 18H02440, M. Furuse), a Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (C) (18K06234, T. Otani), a Japan Society for the Promotion of Science Grant-in--Aid for Young Scientists (B) (16K18544, T. Otani), a Ministry of Education, Culture, Sports, Science and Technology/Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research on Innovative Areas (17H05627, T. Otani), the National Institute of Natural Science Program for Cross-Disciplinary Study (T. Otani), the Inamori Foundation (T. Otani), and the Takeda Science Foundation (M. Furuse and T. Otani). The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Otani et al.
PY - 2019/10/7
Y1 - 2019/10/7
N2 - 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.
AB - 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.
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U2 - 10.1083/JCB.201812157
DO - 10.1083/JCB.201812157
M3 - Article
C2 - 31467165
AN - SCOPUS:85072992254
SN - 0021-9525
VL - 218
SP - 3372
EP - 3396
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 10
ER -