VEGFR-2/Notch signalling regulates angiogenesis in part by driving the remodelling of endothelial cell junctions and by inducing cell migration. Here, we show that VEGF-induced polarized cell elongation increases cell perimeter and decreases the relative VE-cadherin concentration at junctions, triggering polarized formation of actin-driven junction-associated intermittent lamellipodia (JAIL) under control of the WASP/WAVE/ARP2/3 complex. JAIL allow formation of new VE-cadherin adhesion sites that are critical for cell migration and monolayer integrity. Whereas at the leading edge of the cell, large JAIL drive cell migration with supportive contraction, lateral junctions show small JAIL that allow relative cell movement. VEGFR-2 activation initiates cell elongation through dephosphorylation of junctional myosin light chain II, which leads to a local loss of tension to induce JAIL-mediated junctional remodelling. These events require both microtubules and polarized Rac activity. Together, we propose a model where polarized JAIL formation drives directed cell migration and junctional remodelling during sprouting angiogenesis.

Department of Cybernetics Czech Technical University 16627 Prague 6 Czech Republic

Institute of Anatomy and Vascular Biology Westfälische Wilhelms University of Münster Faculty of Medicine D 48149 Münster Germany

Institute of Cell Biology Center for Molecular Biology of Inflammation D 48149 Münster Germany

Max Planck Institute for Molecular Biomedicine and Westfälische Wilhelms University of Münster Faculty of Medicine D 48149 Münster Germany

Walter Brendel Centre of Experimental Medicine University Hospital LMU Munich D 81377 Munich Germany

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