Evidence map›Paper›PMID 23212915›Full record

ArticleThe Journal of biological chemistry2013

Neural Wiskott-Aldrich syndrome protein (N-WASP)-mediated p120-catenin interaction with Arp2-Actin complex stabilizes endothelial adherens junctions.

Charu Rajput, Vidisha Kini, Monica Smith, Pascal Yazbeck, Alejandra Chavez, Tracy Schmidt, Wei Zhang, Nebojsa Knezevic, Yulia Komarova, Dolly Mehta

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
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  11. MicroRNA Expression Profiling in Behçet's Disease.Journal of immunology research · 2018
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  17. Potential implications of interleukin-7 in chronic wound healing.Experimental and therapeutic medicine · 2016
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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

10 authors at 2 institutions in 1 country.

Charu RajputDepartment of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
Vidisha Kini
Monica Smith
Pascal Yazbeck
Alejandra Chavez
Tracy Schmidt
Wei Zhang
Nebojsa Knezevic
Yulia Komarova
Dolly Mehta
University of Illinois Chicago · USUniversity of Illinois Urbana-Champaign · US

Funding

TRPC6 Regulation of Lung Endothelial Barrier FunctionP01HL060678 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MALIK, ASRAR B. · 2000 to 2020
$40.1M
TRAINING PROGRAM IN LUNG BIOLOGY AND PATHOBIOLOGYT32HL007829 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DOLLY MEHTA · 1995 to 2026
$15.6M
Focal Adhesion Kinase Regulation of Lung Vascular Permeability and EdemagenesisR01HL084153 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MEHTA, DOLLY · 2007 to 2022
$5.4M
Rho Regulation of Pulmonary Vascular PermeabilityR01HL071794 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MEHTA, DOLLY · 2003 to 2013
$3.2M
NHLBI NIH HHS HL71794NHLBI NIH HHS HL84153NHLBI NIH HHS P01 HL060678NHLBI NIH HHS R01 HL071794NHLBI NIH HHS R01 HL084153NHLBI NIH HHS T32 HL007829
6 · The paper itself

Abstract

Stable adherens junctions (AJs) are required for formation of restrictive endothelial barrier. Vascular endothelial cadherin from contiguous endothelial cells forms AJs, which are stabilized intracellularly by binding of p120-catenin and cortical actin. Mechanisms inducing cortical actin formation and enabling its linkage with p120-catenin remain enigmatic. We altered the function of neural Wiskott-Aldrich syndrome protein (N-WASP), which induces actin polymerization through actin-related protein 2/3 complex (Arp2/3), to address the role of N-WASP in regulating AJ stability and thereby endothelial permeability. We show that depletion of N-WASP in endothelial cells impaired AJ adhesion and favored the organization of actin from cortical actin to stress fibers, resulting thereby in formation of leaky endothelial barrier. Exposure of the N-WASP-depleted endothelial cell monolayer to the permeability-increasing mediator, thrombin, exaggerated AJ disruption and stress fiber formation, leading to an irreversible increase in endothelial permeability. We show that N-WASP binds p120-catenin through its verprolin cofilin acid (VCA) domain, induces cortical actin formation through Arp2, and links p120-catenin with cortical actin. The interaction of N-WASP with p120-catenin, actin, and Arp2 requires phosphorylation of N-WASP at the Tyr-256 residue by focal adhesion kinase. Expression of the VCA domain of N-WASP or phosphomimicking (Y256D)-N-WASP mutant in endothelial cells stabilizes AJs and facilitates barrier recovery after thrombin stimulation. Our study demonstrates that N-WASP, by mediating p120-catenin interaction with actin-polymerizing machinery, maintains AJs and mitigates disruption of endothelial barrier function by edemagenic agents, therefore representing a novel target for preventing leaky endothelial barrier syndrome.

Indexed as

Actin-Related Protein 2Actin-Related Protein 2-3 ComplexAdherens JunctionsAnimalsCateninsChlorocebus aethiopsCOS CellsDelta CateninEndothelial CellsHumansPhosphorylationProtein BindingProtein Structure, TertiaryStress FibersWiskott-Aldrich Syndrome Protein, NeuronalActin-Related Protein 2Actin-Related Protein 2-3 ComplexACTR2 protein, humanCateninsDelta CateninWASL protein, humanWiskott-Aldrich Syndrome Protein, Neuronal

Identifiers

PMID23212915
PMCPMC3567675
OpenAlexW1975976862

What OpenQuestion holds

Textmetadata
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.