VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis.
J Cell Sci
; 129(21): 4091-4104, 2016 11 01.
Article
en En
| MEDLINE
| ID: mdl-27656109
ABSTRACT
Endocytosis plays a crucial role in receptor signalling. VEGFR2 (also known as KDR) and its ligand VEGFA are fundamental in neovascularisation. However, our understanding of the role of endocytosis in VEGFR2 signalling remains limited. Despite the existence of diverse internalisation routes, the only known endocytic pathway for VEGFR2 is the clathrin-mediated pathway. Here, we show that this pathway is the predominant internalisation route for VEGFR2 only in the absence of ligand. Intriguingly, VEGFA induces a new internalisation itinerary for VEGFR2, the pathway of macropinocytosis, which becomes the prevalent endocytic route for the receptor in the presence of ligand, whereas the contribution of the clathrin-mediated route becomes minor. Macropinocytic internalisation of VEGFR2, which mechanistically is mediated through the small GTPase CDC42, takes place through macropinosomes generated at ruffling areas of the membrane. Interestingly, macropinocytosis plays a crucial role in VEGFA-induced signalling, endothelial cell functions in vitro and angiogenesis in vivo, whereas clathrin-mediated endocytosis is not essential for VEGFA signalling. These findings expand our knowledge on the endocytic pathways of VEGFR2 and suggest that VEGFA-driven internalisation of VEGFR2 through macropinocytosis is essential for endothelial cell signalling and angiogenesis.
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Banco de datos:
MEDLINE
Asunto principal:
Pinocitosis
/
Transducción de Señal
/
Neovascularización Fisiológica
/
Receptor 2 de Factores de Crecimiento Endotelial Vascular
/
Factor A de Crecimiento Endotelial Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article