ZFIN ID: ZDB-PUB-120905-2
Formation of a PKCzeta/beta-catenin complex in endothelial cells promotes angiopoietin-1-induced collective directional migration and angiogenic sprouting
Oubaha, M., Lin, M.I., Margaron, Y., Filion, D., Price, E.N., Zon, L.I., Côté, J.F., and Gratton, J.P.
Angiogenic sprouting requires that cell-cell contacts be maintained during migration of endothelial cells. Angiopoietin-1
(Ang-1) and VEGF act oppositely on endothelial cell junctions. We found that Ang-1 promotes collective and directional migration
and, in contrast to VEGF, induces the formation of a complex formed of atypical PKCζ and β-catenin at cell-cell junctions
and at the leading edge of migrating endothelial cells. This complex brings Par3, Par6 and adherens junction proteins at the
front of migrating cells to locally activate Rac1 in response to Ang-1. The colocalization of PKCζ and β-catenin at leading
edge along with PKCζ-dependent stabilization of cell-cell contacts promotes directed and collective endothelial cell migration.
Consistent with these results, downregulation of PKCζ in endothelial cells alters Ang-1-induced sprouting in vitro and knockdown in developing zebrafish results in intersegmental vessel (ISV) defects caused by a perturbed directionality
of tip cells and by loss of cell contacts between tip and stalk cells. These results reveal that PKCζ and β-catenin function
in a complex at adherens junctions and at the leading edge of migrating endothelial cells to modulate collective and directional
migration during angiogenesis.