TY  - JOUR
A1  - Zink, Joana Miriam
A1  - Frye, Maike
A1  - Frömel, Timo
A1  - Carlantoni, Claudia
A1  - John, David
A1  - Schreier, Danny
A1  - Weigert, Andreas
A1  - Laban, Hebatullah
A1  - Salinas, Gabriela
A1  - Stingl, Heike
A1  - Günther, Lea
A1  - Popp, Rüdiger
A1  - Hu, Jiong
A1  - Vanhollebeke, Benoit
A1  - Schmidt, Hannes
A1  - Acker-Palmer, Amparo
A1  - Renné, Thomas
A1  - Fleming, Ingrid
A1  - Benz, Peter M.
T1  - EVL regulates VEGF receptor-2 internalization and signaling in developmental angiogenesis
T2  - EMBO reports
N2  - 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.
KW  - Ena/VASP proteins
KW  - endothelial cells
KW  - sprouting angiogenesis
KW  - tip cell filopodia formation
KW  - VEGF receptor 2 internalization and signaling
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63881
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-638814
SN  - 1469-3178
N1  - This work was supported by the Deutsche Forschungsgemeinschaft (SFB 834/A8 to PMB, SFB 834/A5 to IF, SFB 1039/B6 to AW, SFB 841/B8, and SFB 877/A11 to TR). PMB was also supported by the German Center for Cardiovascular Research (DZHK B14-028 SE). MF was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 840189 and the Werner-Otto-Stiftung Hamburg (8/95). The authors are indebted to Isabel Winter, Mechtild Piepenbrock-Gyamfi, Katharina Engel-Herbig, and Praveen Mathoor for expert technical assistance (all Johann Wolfgang Goethe University, Frankfurt, Germany). The authors acknowledge Kavi Devraj (Goethe University Frankfurt, Germany) for help with the isolation of brain endothelial cells, Michael Potente (MPI Bad Nauheim, Germany) for scientific input, Marcus Fruttinger (University College, London, UK) for providing pdgf-driven Cre mice, and Bernhard Nieswandt (University of Würzburg, Germany) for providing transgenic FLP-deleter mice. Open Access funding enabled and organized by ProjektDEAL.
VL  - 22
IS  - 2, art. e48961
SP  - 1
EP  - 19
PB  - EMBO Press; Wiley
CY  - Heidelberg; Hoboken, NJ [u.a.]
ER  -