Rho-ROCK liberates sequestered claudin for rapid de novo tight junction formation

Area of Science:

• Cell Biology
• Epithelial Biology
• Biochemistry

Background:

• Epithelial cell sheets act as crucial barriers, requiring continuous maintenance through cell turnover.
• Preserving existing tight junctions (TJs) and forming new ones are vital for sustained barrier function.
• The molecular mechanisms underlying the formation of new (de novo) TJs are not well understood.

Purpose of the Study:

• To investigate the molecular mechanisms of de novo TJ formation in epithelial cell sheets.
• To examine TJ formation during apoptotic cell removal and epidermal differentiation.

Main Methods:

• Utilized mouse monolayer epithelial sheets and stratified epidermis models.
• Investigated the roles of EpCAM/TROP2, claudin, matriptase, and the Rho-ROCK pathway.

Main Results:

• Demonstrated that rapid claudin assembly is regulated by the dissociation of the EpCAM/TROP2-claudin complex.
• Identified the Rho-ROCK pathway as an initiator of matriptase activation.
• Showed that matriptase cleavage of EpCAM/TROP2 supplies polymerizable claudin for de novo TJ formation.

Conclusions:

• The EpCAM/TROP2-claudin complex serves as a reservoir for claudin.
• The Rho-ROCK-matriptase axis is critical for rapid de novo TJ formation and epithelial barrier maintenance.