ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation.
Bottom Line: ZO-1 depletion led to tight junction disruption, redistribution of active myosin II from junctions to stress fibers, reduced tension on VE-cadherin and loss of junctional mechanotransducers such as vinculin and PAK2, and induced vinculin dissociation from the α-catenin-VE-cadherin complex.Claudin-5 depletion only mimicked ZO-1 effects on barrier formation, whereas the effects on mechanotransducers were rescued by inhibition of ROCK and phenocopied by JAM-A, JACOP, or p114RhoGEF down-regulation.ZO-1 was required for junctional recruitment of JACOP, which, in turn, recruited p114RhoGEF.
Affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, London EC1V 9EL, England, UK.Show MeSH
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Mentions: JAM-A was efficiently depleted by two siRNAs and affected the localization of claudin-5 and ZO-1, but not VE-cadherin (Fig. 5). Hence, JAM-A and ZO-1 appear to be linked in a bidirectional, cooperative manner, as each influenced the other’s distribution and both were required for claudin-5 localization at tight junctions. Reduced expression of JAM-A induced redistribution of PAK2 and vinculin from cell contacts to focal adhesions and induction of stress fibers (Fig. 5 C). ZO-1 and JAM-A therefore form a functional unit that regulates tight junction assembly and cytoskeletal organization.
Affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, London EC1V 9EL, England, UK.