Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

Abstract Angiogenesis involves the coordinated growth and migration of endothelial cells (EC) toward a proangiogenic signal. The Wnt Planar Cell Polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here, we report that Kif26b, a kinesin, and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we found that Kif26b is recruited within the Dvl3/Daam1 complex. Using a 3D in vitro angiogenesis assay, we showed that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT-Organizing Center (MTOC)/Golgi and Myosin IIB cell rear enrichment, therefore the cell fails to establish a proper front-rear polarity. Interestingly, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we highlighted that Kif26b functions on MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b together with Dvl3/Daam1 initiates cell polarity through the control of PCP signaling pathway-dependent activation.