GUILLABERT-GOURGUES, Aude; JASPARD-VINASSA, Beatrice; BATS, Marie-Lise; SEWDUTH, Raj N; FRANZL, Nathalie; PEGHAIRE, Claire; JEANNINGROS, Sylvie; MOREAU, Catherine; ROUX, Etienne; LARRIEU-LAHARGUE, Frederic; DUFOURCQ, Pascale; COUFFINHAL, Thierry; DUPLÀA, Cecile

doi:10.1091/mbc.E14-08-1332

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GUILLABERT-GOURGUES, Aude
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

JASPARD-VINASSA, Beatrice
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

BATS, Marie-Lise
Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases

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Ce document a été publié dans

Molecular Biology of the Cell. 2016-03-15, vol. 27, n° 6, p. 941-53

Résumé en anglais

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.< Réduire

Mots clés en anglais

Adaptor Proteins

Signal Transducing

Animals

Cell Movement

Cell Polarity

Dishevelled Proteins

Endothelial Cells

Humans

Kinesins

Mice

Microfilament Proteins

Microtubule-Organizing Center

Microtubules

Neovascularization

Physiologic

Wnt Signaling Pathway

rho GTP-Binding Proteins