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Updated: Jan 20, 2026
Tight Junctions
Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity
Tetsuhisa Otani1,2, Thanh Phuong Nguyen1,2, Shinsaku Tokuda3
1Division of Cell Structure, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
Insights
Tight junctions (TJs) are crucial for epithelial barriers. Claudins and JAM-A coordinate TJ formation and epithelial polarity, clarifying their distinct roles in barrier function.
Area of Science:
- Cell Biology
- Epithelial Biology
- Membrane Protein Function
Background:
- Tight junctions (TJs) are critical for epithelial barrier function and polarity.
- The precise roles of TJ components, such as claudins and scaffolding proteins (ZO-1/ZO-2), in TJ organization and polarity remain incompletely understood.
Purpose of the Study:
- To elucidate the distinct and cooperative roles of TJ components, including claudins, ZO-1/ZO-2, and JAM-A, in the formation of TJ structures, epithelial barriers, and epithelial polarity.
Main Methods:
- Systematic knockout of TJ components using genome editing in epithelial cells.
- Assessment of TJ structure, epithelial barrier integrity (paracellular permeability to electrolytes and macromolecules), and epithelial polarity.
Main Results:
- ZO-1/ZO-2 deficiency abolished TJ structures and epithelial barriers.
- Claudin deficiency disrupted TJ strands and the electrolyte barrier but preserved membrane appositions and the macromolecule barrier, without affecting epithelial polarity.
- Simultaneous knockout of claudins and JAM-A led to loss of membrane appositions, macromolecule barrier defects, and sporadic polarity issues.
Conclusions:
- Claudins and ZO-1/ZO-2 play distinct roles in TJ formation and barrier function.
- Claudins and JAM-A cooperate to establish TJ-mediated membrane appositions and regulate epithelial polarity.
Abstract:
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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