Evidence mapPaperPMID 39013281Full record

ArticleThe Journal of cell biology2024

TLNRD1 is a CCM complex component and regulates endothelial barrier integrity.

Neil J Ball, Sujan Ghimire, Gautier Follain, Ada O Pajari, Diana Wurzinger, Monika Vaitkevičiūtė, Alana R Cowell, Bence Berki, Johanna Ivaska, Ilkka Paatero and 2 more

Abstract read
In one paragraph

Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

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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

12 authors.

Neil J Ball *School of Biosciences, University of Kent, Canterbury, UK.ORCID 0000-0001-7165-6363
Sujan Ghimire *Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0000-0003-3660-4300
Gautier FollainFaculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0000-0003-0495-9529
Ada O PajariFaculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0009-0005-5787-6147
Diana WurzingerFaculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0009-0004-9363-3604
Monika VaitkevičiūtėFaculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0000-0003-1803-9571
Alana R CowellSchool of Biosciences, University of Kent, Canterbury, UK.ORCID 0000-0003-4614-9364
Bence BerkiTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.ORCID 0009-0006-6482-6436
Johanna IvaskaTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.ORCID 0000-0002-6295-6556
Ilkka PaateroTurku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.ORCID 0000-0001-5926-2396
Benjamin T GoultSchool of Biosciences, University of Kent, Canterbury, UK.ORCID 0000-0002-3438-2807
Guillaume JacquemetFaculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.ORCID 0000-0002-9286-920X

Funding

Åbo Akademi UniversityAcademy of Finland 337530Biocenter FinlandBiotechnology and Biological Sciences Research Council BB/S007245/1Cancer Research UK CRUK-A21671Cancer Society of FinlandCentre of Excellence # 346131Finnish Cancer InstituteJane and Aatos Erkko FoundationResearch Council of Finland 338537Sigrid Juselius Foundation
6 · The paper itself

Abstract

We previously identified talin rod domain-containing protein 1 (TLNRD1) as a potent actin-bundling protein in vitro. Here, we report that TLNRD1 is expressed in the vasculature in vivo. Its depletion leads to vascular abnormalities in vivo and modulation of endothelial cell monolayer integrity in vitro. We demonstrate that TLNRD1 is a component of the cerebral cavernous malformations (CCM) complex through its direct interaction with CCM2, which is mediated by a hydrophobic C-terminal helix in CCM2 that attaches to a hydrophobic groove on the four-helix domain of TLNRD1. Disruption of this binding interface leads to CCM2 and TLNRD1 accumulation in the nucleus and actin fibers. Our findings indicate that CCM2 controls TLNRD1 localization to the cytoplasm and inhibits its actin-bundling activity and that the CCM2-TLNRD1 interaction impacts endothelial actin stress fiber and focal adhesion formation. Based on these results, we propose a new pathway by which the CCM complex modulates the actin cytoskeleton and vascular integrity.

Indexed as

Hemangioma, Cavernous, Central Nervous SystemHuman Umbilical Vein Endothelial CellsActin CytoskeletonActinsAnimalsCarrier ProteinsCell NucleusEndothelial CellsFocal AdhesionsHumansMiceProtein BindingStress FibersTalinActinsCarrier ProteinsCCM2 protein, humanTalinTLN1 protein, human

Identifiers

PMID39013281
PMCPMC11252447

What Socratic holds

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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 Socratic graph.