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VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation via macropinocytosis

Basagiannis, D; Zografou, S; Murphy, C; Fotsis, T; Morbidelli, L; Ziche, M; Bleck, C; ... Christoforidis, S; + view all (2016) VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation via macropinocytosis. Journal of Cell Science , 129 (21) pp. 4091-4104. 10.1242/jcs.188219. Green open access

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Abstract

Endocytosis plays critical role in receptor signalling. VEGFR2 and its ligand VEGFA are fundamental in neovascularization. Yet, our understanding of the role of endocytosis in VEGFR2 signalling remains limited. Despite the existence of diverse internalisation routes, the only known endocytic pathway of VEGFR2 is the clathrin-mediated. Here, we show that this pathway is the predominant internalisation route of VEGFR2 only in the absence of ligand. Intriguingly, VEGF introduces a novel internalisation itinerary for VEGFR2, the pathway of macropinocytosis, which becomes the prevalent endocytic route of the receptor in the presence of ligand, while the route of clathrin becomes minor. Macropinocytic internalisation of VEGFR2, which mechanistically is mediated via the small GTPase CDC42, takes place via macropinosomes generated at ruffling areas of the membrane. Interestingly, macropinocytosis plays critical role in VEGF-induced signalling, endothelial cell functions in vitro and angiogenesis in vivo, while clathrin-mediated endocytosis is not essential for VEGF signalling. These findings expand our knowledge on the endocytic pathways of VEGFR2 and suggest that VEGF-driven internalisation of VEGFR2 via macropinocytosis is essential for endothelial cell signalling and angiogenesis.

Type: Article
Title: VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation via macropinocytosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.188219
Publisher version: http://doi.org/10.1242/jcs.188219
Language: English
Additional information: © 2016. Published by The Company of Biologists Ltd http://www.biologists.com/user-licence-1-1/.
Keywords: Endocytosis, Macropinocytosis, Membrane trafficking, Signalling, VEGFVEGFR2
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1517747
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