title: 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 (ECs) 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 find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show 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. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in 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.
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Guillabert-Gourgues
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Jaspard-Vinassa
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France.
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Bats
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Sewduth
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franzl
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Peghaire
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jeanningros
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Moreau
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Roux
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Larrieu-Lahargue
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France Service des Maladies Cardiaques et Vasculaires, Centre Hospitalier Universitaire de Bordeaux, F-33000 Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Couffinhal
authors.affiliation: Adaptation Cardiovasculaire à l'Ischémie, INSERM, U1034, F-33600 Pessac, France Adaptation Cardiovasculaire à l'Ischémie, U1034, Université de Bordeaux, F-33600 Pessac, France cecile.duplaa@inserm.fr.
authors.forename: Cecile
authors.initials: C
authors.lastname: Duplàa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D000072261:Dishevelled Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D018919:Neovascularization, Physiologic; D060449:Wnt Signaling Pathway; D020741:rho GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C499094:DAAM1 protein, human; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; C487946:KIF26B protein, mouse; D008840:Microfilament Proteins; D016547:Kinesins; D020741:rho GTP-Binding Proteins