PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function

Area of Science:

• Cell Biology
• Epithelial Biology
• Biochemistry

Background:

• Cell-cell junctions are vital for epithelial integrity and barrier function.
• Mechanisms regulating junction remodeling are not fully understood.

Purpose of the Study:

• Investigate the role of junctional kinase PAK4 in vertex remodeling.
• Elucidate the interplay between PAK4 and scaffolding protein Afadin in maintaining epithelial integrity.

Main Methods:

• Utilized MDCK cells and Xenopus embryos for experiments.
• Employed PAK4 inhibition and knockout strategies.
• Performed live imaging and Afadin knockout (Afdn-KO) experiments.

Main Results:

• PAK4 localizes to apical junctions and vertices, with Afadin mediating its recruitment.
• PAK4 inhibition or knockout leads to increased higher-order vertices, junctional discontinuities, and impaired barrier function.
• Restoring PAK4 in Afdn-KO cells partially rescues junctional continuity and barrier function.

Conclusions:

• PAK4 and Afadin collaboratively promote vertex remodeling essential for epithelial integrity.
• This cooperation ensures proper barrier function and prevents epithelial leakage.
• Dysregulation of PAK4 and Afadin compromises epithelial barrier properties.