J Cell Biol 2026 Jul 07;2259:. doi: 10.1083/jcb.202510024.

PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function.

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Cell-cell junctions are essential for epithelial integrity and barrier function, but the mechanisms regulating their remodeling remain unclear. Here, we investigated the role of the junctional kinase PAK4 in vertex remodeling. PAK4 accumulated at multicellular vertices in MDCK cells and Xenopus embryos. Inhibition or knockout (KO) of PAK4 increased the number of higher-order vertices, caused junctional discontinuities, and impaired barrier function in MDCK cells. PAK4 recruitment required the scaffolding protein Afadin. Severe junctional defects and reduced barrier function in Afdn-KO cells were partially rescued by artificial PAK4 targeting. In Xenopus embryos, PAK4 showed dynamic accumulation at remodeling vertices, and PAK4 inhibition hindered vertex remodeling. Expression of an amino-terminal fragment (PAK4-NT) impaired remodeling, induced cytokinetic failure, and caused barrier leakage at multicellular vertices. In both systems, PAK4-deficient cells exhibited abnormal accumulation of junctional myosin II, likely due to reduced myosin phosphatase activity. These findings indicate that PAK4 and Afadin cooperate to maintain epithelial integrity and barrier function by promoting vertex remodeling.

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Species referenced: Xenopus laevis