Evidence map›Paper›PMID 31138815›Full record

ArticleNature communications2019

Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis.

Gael Genet, Kevin Boyé, Thomas Mathivet, Roxana Ola, Feng Zhang, Alexandre Dubrac, Jinyu Li, Nafiisha Genet, Luiz Henrique Geraldo, Lorena Benedetti and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 92 citations in OpenAlex.

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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 3 countries.

Gael GenetCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Kevin BoyéCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Thomas MathivetInserm U970, Paris Cardiovascular Research Center, Paris, 75015, France.ORCID http://orcid.org/0000-0001-7761-1684
Roxana OlaCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Feng ZhangCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Alexandre DubracCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0002-3829-2577
Jinyu LiCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Nafiisha GenetCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Luiz Henrique GeraldoInserm U970, Paris Cardiovascular Research Center, Paris, 75015, France.ORCID http://orcid.org/0000-0003-3318-4697
Lorena BenedettiDepartment of Neuroscience and Cell Biology, School of Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Steffen KünzelCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Laurence Pibouin-FragnerInserm U970, Paris Cardiovascular Research Center, Paris, 75015, France.
Jean-Leon ThomasCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
Anne EichmannCardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA. anne.eichmann@yale.edu.
Yale University · USInserm · FR

Funding

Yale Core Grant for Vision ResearchP30EY026878 · NEI · YALE UNIVERSITY · PI In-Jung Kim · 2016 to 2026
$7.1M
MOLECULAR MECHANISMS IN SYNAPTIC VESICLE RECYCLINGR01NS036251 · NINDS · YALE UNIVERSITY · PI DE CAMILLI, PIETRO · 1997 to 2021
$4.7M
Targeting endothelial migration to prevent neovascularizationR01HL125811 · NHLBI · YALE UNIVERSITY · PI EICHMANN, ANNE CHRISTINE · 2015 to 2025
$4.1M
Molecular Mechanisms in Synaptic Vesicle RecyclingR37NS036251 · NINDS · YALE UNIVERSITY · PI DE CAMILLI, PIETRO · 2010 to 2016
$2.7M
Novel approaches to manipulate sprouting angiogenesisR01EY025979 · NEI · YALE UNIVERSITY · PI EICHMANN, ANNE CHRISTINE · 2015 to 2019
$1.9M
Novel approached to prevent diet-induced obesity via lacteal junctionsR01DK120373 · NIDDK · YALE UNIVERSITY · PI EICHMANN, ANNE CHRISTINE · 2019 to 2022
$1.5M
Agence Nationale de la Recherche (French National Research Agency) 17-CE14-0005-03American Heart Association (American Heart Association, Inc.) 17SDG33700124American Heart Association (American Heart Association, Inc.) 18POST34070074American Heart Association-American Stroke Association 18POST34070074NEI NIH HHS P30 EY026878NEI NIH HHS R01 EY025979NHLBI NIH HHS R01 HL125811NIDDK NIH HHS R01 DK120373NINDS NIH HHS R01 NS036251NINDS NIH HHS R37 NS036251U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY025979U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HLI125811
6 · The paper itself

Abstract

Endothelial cell migration, proliferation and survival are triggered by VEGF-A activation of VEGFR2. However, how these cell behaviors are regulated individually is still unknown. Here we identify Endophilin-A2 (ENDOA2), a BAR-domain protein that orchestrates CLATHRIN-independent internalization, as a critical mediator of endothelial cell migration and sprouting angiogenesis. We show that EndoA2 knockout mice exhibit postnatal angiogenesis defects and impaired front-rear polarization of sprouting tip cells. ENDOA2 deficiency reduces VEGFR2 internalization and inhibits downstream activation of the signaling effector PAK but not ERK, thereby affecting front-rear polarity and migration but not proliferation or survival. Mechanistically, VEGFR2 is directed towards ENDOA2-mediated endocytosis by the SLIT2-ROBO pathway via SLIT-ROBO-GAP1 bridging of ENDOA2 and ROBO1. Blocking ENDOA2-mediated endothelial cell migration attenuates pathological angiogenesis in oxygen-induced retinopathy models. This work identifies a specific endocytic pathway controlling a subset of VEGFR2 mediated responses that could be targeted to prevent excessive sprouting angiogenesis in pathological conditions.

Indexed as

AcyltransferasesAnimalsCell MovementCell PolarityCell ProliferationCell SurvivalEndocytosisEndothelial CellsIntercellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMiceMice, KnockoutNeovascularization, PhysiologicNerve Tissue Proteinsp21-Activated KinasesReceptors, Immunologic2-acylglycerophosphate acyltransferaseAcyltransferasesIntercellular Signaling Peptides and ProteinsKdr protein, mouseNerve Tissue Proteinsp21-Activated KinasesReceptors, ImmunologicRoundabout ProteinsSlit Homolog 2 ProteinVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID31138815
PMCPMC6538628
OpenAlexW2946976931

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.