ZO-1 shuttles between apical junctional complexes and podosomes by riding ERK activation waves

Collective cell migration is essential in various physiological processes, including embryonic development, wound healing, and cancer metastasis. However, the mechanisms by which individual cells achieve coordinated movement remain elusive. Here, we demonstrate that zonula occludens-1 (ZO-1), a scaffolding protein of tight junctions (TJs), dynamically translocates to form cell-extracellular matrix (ECM) adhesion complexes, podosomes, at the basal cell surface during migration. Extracellular signal-regulated kinase (ERK) activation triggers the translocation of ZO-1 to podosomes, where ZO-1 promotes invasive migration. ZO-1 also contributes to ERK activation dynamics within the cell collective, thereby influencing collective migratory behavior. In this work, we elucidate the dual roles of ZO-1 in coordinating intercellular signaling and invasive movement, providing insights into the mechanisms that integrate individual cell behaviors into a cohesive collective migration.