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: We established a loss-of-function approach to determine the role of ZO-1 in EC using HDMEC. HDMEC were chosen because we found them to form robust and regular junctional complexes. Two distinct siRNAs were identified that effectively down-regulated ZO-1 (Fig. 1, A and B).
Affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, London EC1V 9EL, England, UK.