Formation of a PKCζ/β-catenin complex in endothelial cells promotes angiopoietin-1–induced collective directional migration and angiogenic sprouting

Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration

“…These changes in morphology and architectural organization of cells are orchestrated by the polarized activation of Cdc42 and its downstream effector the polarity complex Par6/PKCζ 69 . During angiogenic sprouting elicited by angiopoitin-1, which induces collective and directional migration of endothelial cells, a signaling complex that includes β-catenin and Par3/Par6/PKCζ is recruited to the cell front to coordinate localized activation of Rac by Tiam1, a Rac-specific GEF 70 . Interestingly, this complex is also functional in adherens junctions where it might promote stabilization of cell-cell contacts 70 .…”

“…During angiogenic sprouting elicited by angiopoitin-1, which induces collective and directional migration of endothelial cells, a signaling complex that includes β-catenin and Par3/Par6/PKCζ is recruited to the cell front to coordinate localized activation of Rac by Tiam1, a Rac-specific GEF 70 . Interestingly, this complex is also functional in adherens junctions where it might promote stabilization of cell-cell contacts 70 . Consistent with this notion, a recent study demonstrated full activation of the VEGFR at the sprout tip but not in the stalk cells in which inactivation the VEGFR is mediated by Tie2-dependent targeting of vascular endothelia phosphotyrosine phosphatase (VE-PTP) to cell-cell junctions 71 .…”

Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer

“…Ang1-Tie2 complexes assemble in trans at EC-EC junctions, promoting EC-EC adhesion and EC survival. Ang1 also promotes collective directional migration of ECs by relocating atypical PKCζ to the leading EC edge, where it forms a complex with β-catenin that interacts with polarity proteins at adherens junctions (19). In atypical PKCζ morphant zebrafish, tip cells, after initial sprouting from the aorta, separate from the secondary connector stalk cells and lose polarity cues by extending filopodia more randomly (Figure 2).…”

Making Heads or Tails of It: Cell–Cell Adhesion in Cellular and Supracellular Polarity in Collective Migration

“…An example of cross talk involving a bcatenin-aPKC complex has been observed during endothelial sprouting. On angiopoietin-1 stimulation, this complex localizes to both the cell front to activate Rac, and to the rear, where it stabilizes cell -cell adhesion, and thus promotes both front -rear polarization and cohesion of the migrating branch (Oubaha et al 2012).…”

“…The asymmetric distribution of cadherin-based adherens junctions resulting from their absence at the front is a distinguishing feature of leader cells and is sufficient to induce front -rear polarization of the cytoskeleton and the cytoplasm in vivo and in vitro (Desai et al 2009;Dupin et al 2009;Ozaki et al 2010;Dumortier et al 2012;Ng et al 2012;Oubaha et al 2012;Weberet al 2012). …”