Evidence map›Paper›PMID 27139341›Full record

ArticleJournal of molecular and cellular cardiology2016

Thin filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and nebulin.

Justin Kolb, Frank Li, Mei Methawasin, Maya Adler, Yael-Natalie Escobar, Joshua Nedrud, Christopher T Pappas, Samantha P Harris, Henk Granzier

Abstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-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

25 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. Fine tuning contractility: atrial sarcomere function in health and disease.American journal of physiology. Heart and circulatory physiology · 2024
    Review
  6. A human FLII gene variant alters sarcomeric actin thin filament length and predisposes to cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022
    Review
  8. Review
  9. Article
  10. Article
  11. Alpha and beta myosin isoforms and human atrial and ventricular contraction.Cellular and molecular life sciences : CMLS · 2021
    Review
  12. Article
  13. Article
  14. Nebulin: big protein with big responsibilities.Journal of muscle research and cell motility · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Sarcomere length-dependent effects on CaThe Journal of general physiology · 2019
    Article
  19. Article
  20. Article
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

9 authors at 1 institution in 1 country.

Justin KolbDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Frank LiDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Mei MethawasinDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Maya AdlerDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Yael-Natalie EscobarDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Joshua NedrudDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Christopher T PappasDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Samantha P HarrisDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA.
Henk GranzierDepartment of Cellular and Molecular Medicine, Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, USA. Electronic address: granzier@email.arizona.edu.
University of Arizona · US

Funding

MARC/Biomedical Research and Training Program at the University of ArizonaT34GM008718 · NIGMS · UNIVERSITY OF ARIZONA · PI MIRANDA, KATRINA M. · 1999 to 2021
$8.6M
Role of Myosin Binding Protein-C in the Regulation of Myocardial ContractionR01HL080367 · NHLBI · UNIVERSITY OF WASHINGTON · PI Samantha P Harris · 2005 to 2026
$7.5M
Roles of Nebulin in Structure and Function of Striated MuscleR01AR053897 · NIAMS · UNIVERSITY OF ARIZONA · PI Henk L. GRANZIER · 2007 to 2026
$7.4M
Function of Giant Sarcomere Matrix Proteins in MuscleR01HL062881 · NHLBI · WASHINGTON STATE UNIVERSITY · PI GRANZIER, HENK L. · 1999 to 2018
$6.4M
Deciphering the role of Lmod2 in thin filament length regulation and dilated cardiomyopathyR01HL123078 · NHLBI · UNIVERSITY OF ARIZONA · PI Carol C Gregorio, Shashank Shekhar · 2015 to 2026
$5.6M
NHLBI NIH HHS R01 HL062881NHLBI NIH HHS R01 HL080367NHLBI NIH HHS R01 HL123078NIAMS NIH HHS R01 AR053897NIGMS NIH HHS T34 GM008718
6 · The paper itself

Abstract

Thin filament length (TFL) is an important determinant of the force-sarcomere length (SL) relation of cardiac muscle. However, the various mechanisms that control TFL are not well understood. Here we tested the previously proposed hypothesis that the actin-binding protein nebulin contributes to TFL regulation in the heart by using a cardiac-specific nebulin cKO mouse model (αMHC Cre Neb cKO). Atrial myocytes were studied because nebulin expression has been reported to be most prominent in this cell type. TFL was measured in right and left atrial myocytes using deconvolution optical microscopy and staining for filamentous actin with phalloidin and for the thin filament pointed-end with an antibody to the capping protein Tropomodulin-1 (Tmod1). Results showed that TFLs in Neb cKO and littermate control mice were not different. Thus, deletion of nebulin in the heart does not alter TFL. However, TFL was found to be ~0.05μm longer in the right than in the left atrium and Tmod1 expression was increased in the right atrium. We also tested the hypothesis that the length of titin's spring region is a factor controlling TFL by studying the Rbm20(ΔRRM) mouse which expresses titins that are ~500kDa (heterozygous mice) and ~1000kDa (homozygous mice) longer than in control mice. Results revealed that TFL was not different in Rbm20(ΔRRM) mice. An unexpected finding in all genotypes studied was that TFL increased as sarcomeres were stretched (~0.1μm per 0.35μm of SL increase). This apparent increase in TFL reached a maximum at a SL of ~3.0μm where TFL was ~1.05μm. The SL dependence of TFL was independent of chemical fixation or the presence of cardiac myosin-binding protein C (cMyBP-C). In summary, we found that in cardiac myocytes TFL varies with SL in a manner that is independent of the size of titin or the presence of nebulin.

Indexed as

AnimalsConnectinMiceMice, KnockoutMicrofilament ProteinsMicroscopyMuscle ProteinsMyocytes, CardiacMyofibrilsMyosin Heavy ChainsSarcomeresConnectinMicrofilament ProteinsMuscle ProteinsMyosin Heavy ChainsnebulinCardiac myocyteLength regulationMyofilamentNebulinThin filamentTitin

Identifiers

PMID27139341
PMCPMC5584371
OpenAlexW2343585259

What OpenQuestion 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 OpenQuestion graph.