Evidence map›Paper›PMID 26403541›Full record

ArticleNature communications2015

Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function.

Parveen Sharma, Cynthia Abbasi, Savo Lazic, Allen C T Teng, Dingyan Wang, Nicole Dubois, Vladimir Ignatchenko, Victoria Wong, Jun Liu, Toshiyuki Araki and 11 more

Open access · goldAbstract read
PubMed Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

33 citing papers in PubMed, 51 citations in OpenAlex.

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  18. The quest of cell surface markers for stem cell therapy.Cellular and molecular life sciences : CMLS · 2021
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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

21 authors at 9 institutions in 2 countries.

Parveen SharmaDepartment of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
Cynthia AbbasiDepartment of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
Savo LazicDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Allen C T TengDepartment of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
Dingyan WangDepartment of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
Nicole DuboisMcEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Vladimir IgnatchenkoPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Victoria WongDepartments of Molecular Genetics and Biochemistry, Donnelly Centre,, University of Toronto, Toronto, Ontario, Canada M5S 3E1.
Jun LiuDepartment of Mechanical and Industrial Engineering, Advanced Micro and Nanosystems Laboratory, University of Toronto, Toronto, Ontario, Canada M5S 3G8.
Toshiyuki ArakiPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Malte TiburcyInstitute of Pharmacology, University Medical Center Göttingen and DZHK (German Center for Cardiovascular Research) partner site Göttingen, Göttingen 37075, Germany.
Cameron AckerleyThe Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Wolfram H ZimmermannInstitute of Pharmacology, University Medical Center Göttingen and DZHK (German Center for Cardiovascular Research) partner site Göttingen, Göttingen 37075, Germany.
Robert HamiltonThe Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Yu SunDepartment of Mechanical and Industrial Engineering, Advanced Micro and Nanosystems Laboratory, University of Toronto, Toronto, Ontario, Canada M5S 3G8.
Peter P LiuToronto General Hospital, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Gordon KellerMcEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Igor StagljarDepartments of Molecular Genetics and Biochemistry, Donnelly Centre,, University of Toronto, Toronto, Ontario, Canada M5S 3E1.
Ian C ScottDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Thomas KislingerPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada M5G 1L7.
Anthony O GramoliniDepartment of Physiology, University of Toronto, Toronto General Hospital Research Institute, Toronto, Ontario, Canada M5G 1L7.
University of Toronto · CAUniversity Health Network · CAHospital for Sick Children · CAToronto General Hospital · CAPrincess Margaret Cancer Centre · CATed Rogers Centre for Heart Research · CAToronto General Hospital Research InstituteUniversitätsmedizin Göttingen · DEUniversity of Göttingen · DE

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Canadian Institutes of Health Research 86663Canadian Institutes of Health Research MOP-106538NHLBI NIH HHS U01 HL099997
6 · The paper itself

Abstract

Membrane proteins are crucial to heart function and development. Here we combine cationic silica-bead coating with shotgun proteomics to enrich for and identify plasma membrane-associated proteins from primary mouse neonatal and human fetal ventricular cardiomyocytes. We identify Tmem65 as a cardiac-enriched, intercalated disc protein that increases during development in both mouse and human hearts. Functional analysis of Tmem65 both in vitro using lentiviral shRNA-mediated knockdown in mouse cardiomyocytes and in vivo using morpholino-based knockdown in zebrafish show marked alterations in gap junction function and cardiac morphology. Molecular analyses suggest that Tmem65 interaction with connexin 43 (Cx43) is required for correct localization of Cx43 to the intercalated disc, since Tmem65 deletion results in marked internalization of Cx43, a shorter half-life through increased degradation, and loss of Cx43 function. Our data demonstrate that the membrane protein Tmem65 is an intercalated disc protein that interacts with and functionally regulates ventricular Cx43.

Indexed as

AnimalsBlotting, WesternChromatography, High Pressure LiquidConnexin 43Fluorescent Antibody TechniqueGap JunctionsGene Knockdown TechniquesHeart Conduction SystemHeart VentriclesIn Vitro TechniquesMembrane ProteinsMiceMicroscopy, ElectronMyocytes, CardiacProteomicsSilicon DioxideConnexin 43Membrane ProteinsSilicon DioxideTmem65 protein, mousetmem65 protein, zebrafishZebrafish Proteins

Identifiers

PMID26403541
OpenAlexW2253173155

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.