Evidence map›Paper›PMID 28910325›Full record

ArticlePloS one2017

Src- and Fyn-dependent apical membrane trafficking events control endothelial lumen formation during vascular tube morphogenesis.

Dae Joong Kim, Pieter R Norden, Jocelynda Salvador, David M Barry, Stephanie L K Bowers, Ondine Cleaver, George E Davis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Dae Joong KimDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Dalton Cardiovascular Research Center, Columbia, MO, United States of America.
Pieter R NordenDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Dalton Cardiovascular Research Center, Columbia, MO, United States of America.
Jocelynda SalvadorDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Dalton Cardiovascular Research Center, Columbia, MO, United States of America.
David M BarryDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas TX, United States of America.
Stephanie L K BowersDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Dalton Cardiovascular Research Center, Columbia, MO, United States of America.
Ondine CleaverDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas TX, United States of America.
George E DavisDepartment of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Dalton Cardiovascular Research Center, Columbia, MO, United States of America.ORCID http://orcid.org/0000-0002-1549-1610
University of Missouri · USSouthwestern Medical Center · US

Funding

Molecular regulation of Rho and Ras family GTPase activity controls vascular lumen formation.R01HL126518 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B, DAVIS, GEORGE E · 2015 to 2023
$3.1M
Priming of vascular tube morphogenesis: Novel role for VEGF and downstreamRhoA activationR01HL136139 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI CLEAVER, ONDINE B, DAVIS, GEORGE E · 2017 to 2020
$1.6M
Novel growth factor and signaling requirements for human capillary tube assemblyR01HL128584 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI DAVIS, GEORGE E · 2015 to 2018
$1.5M
NHLBI NIH HHS R01 HL126518NHLBI NIH HHS R01 HL128584NHLBI NIH HHS R01 HL136139
6 · The paper itself

Abstract

Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases. Functional blockade of Src kinases completely blocks EC lumen and tube formation, whether this occurs during vasculogenic tube assembly or angiogenic sprouting events. Multiple Src kinases participate in this apical membrane formation process and siRNA suppression of Src, Fyn and Yes, but not Lyn, blocks EC lumen formation. We also demonstrate strong apical targeting of Src-GFP and Fyn-GFP fusion proteins and increasing their expression enhances lumen formation. Finally, we show that Src- and Fyn-associated vacuoles track and fuse along a subapically polarized microtubule cytoskeleton, which is highly acetylated. These vacuoles generate the apical luminal membrane in a stereotypically polarized, perinuclear position. Overall, our study identifies a critical role for Src kinases in creating and decorating the EC apical membrane surface during early and late stages of lumen and tube formation, a central event in the molecular control of vascular morphogenesis.

Indexed as

AnimalsCell MembraneEndothelial CellsEndothelium, VascularHumansHuman Umbilical Vein Endothelial CellsMiceNeovascularization, PhysiologicPhosphorylationProtein TransportProto-Oncogene Proteins c-fynSignal Transductionsrc-Family KinasesVacuolesFYN protein, humanProto-Oncogene Proteins c-fynsrc-Family Kinases

Identifiers

PMID28910325
PMCPMC5598984
OpenAlexW2754139911

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.