Evidence map›Paper›PMID 24413171›Full record

ArticleJournal of cell science2014

Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin-43-containing gap junctions in cardiac myocytes.

Alice E Zemljic-Harpf, Joseph C Godoy, Oleksandr Platoshyn, Elizabeth K Asfaw, Anna R Busija, Andrea A Domenighetti, Robert S Ross

Open access · greenAbstract read
In one paragraph

Article in Journal of cell science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

45 citing papers in PubMed, 70 citations in OpenAlex.

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  12. Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022
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  15. Article
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  19. Adenovirus targets transcriptional and posttranslational mechanisms to limit gap junction function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  20. Review
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.

Alice E Zemljic-HarpfVeterans Administration Healthcare San Diego, San Diego, CA 92161, USA.
Joseph C Godoy
Oleksandr Platoshyn
Elizabeth K Asfaw
Anna R Busija
Andrea A Domenighetti
Robert S Ross
University of California, San Diego · USUnited States Department of Veterans Affairs · US

Funding

Vinculin and Talin in Cardiocyte Integrity and AdhesionP01HL046345 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KNOWLTON, KIRK U · 1992 to 2011
$25.0M
Cardiomyocyte mechanotransduction through the integrin complexR01HL103566 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI OMENS, JEFFREY H., ROSS, ROBERT SCOTT · 2010 to 2014
$1.9M
Integrin Function in Cardiac RemodelingR01HL088390 · NHLBI · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI ROSS, ROBERT SCOTT · 2008 to 2011
$1.5M
NHLBI NIH HHS P01 HL046345NHLBI NIH HHS P01 HL 46345NHLBI NIH HHS R01 HL088390NHLBI NIH HHS R01 HL103566
6 · The paper itself

Abstract

Vinculin (Vcl) links actin filaments to integrin- and cadherin-based cellular junctions. Zonula occludens-1 (ZO-1, also known as TJP1) binds connexin-43 (Cx43, also known as GJA1), cadherin and actin. Vcl and ZO-1 anchor the actin cytoskeleton to the sarcolemma. Given that loss of Vcl from cardiomyocytes causes maldistribution of Cx43 and predisposes cardiomyocyte-specific Vcl-knockout mice with preserved heart function to arrhythmia and sudden death, we hypothesized that Vcl and ZO-1 interact and that loss of this interaction destabilizes gap junctions. We found that Vcl, Cx43 and ZO-1 colocalized at the intercalated disc. Loss of cardiomyocyte Vcl caused parallel loss of ZO-1 from intercalated dics. Vcl co-immunoprecipitated Cx43 and ZO-1, and directly bound ZO-1 in yeast two-hybrid studies. Excision of the Vcl gene in neonatal mouse cardiomyocytes caused a reduction in the amount of Vcl mRNA transcript and protein expression leading to (1) decreased protein expression of Cx43, ZO-1, talin, and β1D-integrin, (2) reduced PI3K activation, (3) increased activation of Akt, Erk1 and Erk2, and (4) cardiomyocyte necrosis. In summary, this is the first study showing a direct interaction between Vcl and ZO-1 and illustrates how Vcl plays a crucial role in stabilizing gap junctions and myocyte integrity.

Indexed as

AnimalsCell CommunicationCell MembraneCells, CulturedConnexin 43Gap JunctionsMiceMice, KnockoutMyocytes, CardiacNecrosisPhosphatidylinositol 3-KinasesProtein BindingProtein Interaction Domains and MotifsProtein StabilityProtein TransportTwo-Hybrid System TechniquesConnexin 43Phosphatidylinositol 3-KinasesTjp1 protein, mouseVinculinZonula Occludens-1 ProteinCardiac myocyteGap junctionHeartVclVinculinZO-1Zonula occludens-1

Identifiers

PMID24413171
PMCPMC3937777
OpenAlexW2143169044

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.