EVL regulates VEGF receptor-2 internalization and signaling in developmental angiogenesis.
Ena/VASP proteins
VEGF receptor 2 internalization and signaling
endothelial cells
sprouting angiogenesis
tip cell filopodia formation
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
28
07
2019
revised:
03
12
2020
accepted:
09
12
2020
pubmed:
30
1
2021
medline:
1
6
2021
entrez:
29
1
2021
Statut:
ppublish
Résumé
Endothelial tip cells are essential for VEGF-induced angiogenesis, but underlying mechanisms are elusive. The Ena/VASP protein family, consisting of EVL, VASP, and Mena, plays a pivotal role in axon guidance. Given that axonal growth cones and endothelial tip cells share many common features, from the morphological to the molecular level, we investigated the role of Ena/VASP proteins in angiogenesis. EVL and VASP, but not Mena, are expressed in endothelial cells of the postnatal mouse retina. Global deletion of EVL (but not VASP) compromises the radial sprouting of the vascular plexus in mice. Similarly, endothelial-specific EVL deletion compromises the radial sprouting of the vascular plexus and reduces the endothelial tip cell density and filopodia formation. Gene sets involved in blood vessel development and angiogenesis are down-regulated in EVL-deficient P5-retinal endothelial cells. Consistently, EVL deletion impairs VEGF-induced endothelial cell proliferation and sprouting, and reduces the internalization and phosphorylation of VEGF receptor 2 and its downstream signaling via the MAPK/ERK pathway. Together, we show that endothelial EVL regulates sprouting angiogenesis via VEGF receptor-2 internalization and signaling.
Identifiants
pubmed: 33512764
doi: 10.15252/embr.201948961
pmc: PMC7857432
doi:
Substances chimiques
Cell Adhesion Molecules
0
Evl protein, mouse
0
Kdr protein, mouse
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e48961Informations de copyright
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.
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