Evidence map›Paper›PMID 29316444›Full record

ArticleDevelopmental cell2018

Force Generation via β-Cardiac Myosin, Titin, and α-Actinin Drives Cardiac Sarcomere Assembly from Cell-Matrix Adhesions.

Anant Chopra, Matthew L Kutys, Kehan Zhang, William J Polacheck, Calvin C Sheng, Rebeccah J Luu, Jeroen Eyckmans, J Travis Hinson, Jonathan G Seidman, Christine E Seidman and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing 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

99 citing papers in PubMed.

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  19. A transcriptional enhancer regulates cardiac maturation.Nature cardiovascular research · 2024
    Article
  20. Article

39 more citing papers are in PubMed but not listed here.

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

11 authors.

Anant ChopraDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Matthew L KutysDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Kehan ZhangDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
William J PolacheckDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Calvin C ShengDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Rebeccah J LuuDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Jeroen EyckmansDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
J Travis HinsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Cardiology Center, University of Connecticut Health, Farmington, CT 06030, USA. Electronic address: travis.hinson@jax.org.
Jonathan G SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: seidman@genetics.med.harvard.edu.
Christine E SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: cseidman@genetics.med.harvard.edu.
Christopher S ChenDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA. Electronic address: chencs@bu.edu.

Funding

Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
Molecular Signaling in Hypertrophic CardiomyopathyR01HL084553 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2007 to 2022
$5.9M
Translational Research in Regenerative MedicineT32EB005583 · NIBIB · RUTGERS, THE STATE UNIV OF N.J. · PI LEE, KIBUM, PAREKKADAN, BIJU · 2006 to 2022
$4.7M
Organ Design and Engineering Training Program (ODET Program)T32EB016652 · NIBIB · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2014 to 2023
$3.5M
Metabolic and developmental regulation by AMPK in PRKAG2-associated cardiomyopathyK08HL125807 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HINSON, JOHN TRAVIS · 2015 to 2019
$803k
Modulation of vascular permeability by shear stress via Notch signalingF32HL129733 · NHLBI · HARVARD UNIVERSITY · PI POLACHECK, WILLIAM J · 2016 to 2017
$108k
Howard Hughes Medical InstituteNHLBI NIH HHS F32 HL129733NHLBI NIH HHS K08 HL125807NHLBI NIH HHS R01 HL080494NHLBI NIH HHS R01 HL084553NIBIB NIH HHS T32 EB005583NIBIB NIH HHS T32 EB016652
6 · The paper itself

Abstract

Truncating mutations in the sarcomere protein titin cause dilated cardiomyopathy due to sarcomere insufficiency. However, it remains mechanistically unclear how these mutations decrease sarcomere content in cardiomyocytes. Utilizing human induced pluripotent stem cell-derived cardiomyocytes, CRISPR/Cas9, and live microscopy, we characterize the fundamental mechanisms of human cardiac sarcomere formation. We observe that sarcomerogenesis initiates at protocostameres, sites of cell-extracellular matrix adhesion, where nucleation and centripetal assembly of α-actinin-2-containing fibers provide a template for the fusion of Z-disk precursors, Z bodies, and subsequent striation. We identify that β-cardiac myosin-titin-protocostamere form an essential mechanical connection that transmits forces required to direct α-actinin-2 centripetal fiber assembly and sarcomere formation. Titin propagates diastolic traction stresses from β-cardiac myosin, but not α-cardiac myosin or non-muscle myosin II, to protocostameres during sarcomerogenesis. Ablating protocostameres or decoupling titin from protocostameres abolishes sarcomere assembly. Together these results identify the mechanical and molecular components critical for human cardiac sarcomerogenesis.

Indexed as

ActininAdolescentAdultCell-Matrix JunctionsCells, CulturedConnectinHumansInduced Pluripotent Stem CellsMaleMiddle AgedMyocytes, CardiacSarcomeresVentricular MyosinsActininConnectinTTN protein, humanVentricular Myosinscardiomyocytecardiomyopathyfocal adhesioninduced pluripotent stem cells (IPSCs)mechanotransductionsarcomerogenesistitinβ-cardiac myosin

Identifiers

PMID29316444
PMCPMC6421364

What OpenQuestion holds

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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.