Evidence map›Paper›PMID 34932950›Full record

ArticleDevelopmental cell2021

ERK1/2 inhibition promotes robust myotube growth via CaMKII activation resulting in myoblast-to-myotube fusion.

Tamar Eigler, Giulia Zarfati, Emmanuel Amzallag, Sansrity Sinha, Nadav Segev, Yishaia Zabary, Assaf Zaritsky, Avraham Shakked, Kfir-Baruch Umansky, Eyal D Schejter and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 101 citations in OpenAlex.

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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

13 authors at 3 institutions in 2 countries.

Tamar EiglerDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Giulia ZarfatiDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Emmanuel AmzallagDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Sansrity SinhaDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Nadav SegevDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Yishaia ZabaryDepartment of Software & Information Systems Engineering, Ben Gurion University, Be'er Sheva, Israel.
Assaf ZaritskyDepartment of Software & Information Systems Engineering, Ben Gurion University, Be'er Sheva, Israel.
Avraham ShakkedDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Kfir-Baruch UmanskyDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Eyal D SchejterDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Douglas P MillayDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Eldad TzahorDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address: eldad.tzahor@weizmann.ac.il.
Ori AvinoamDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel. Electronic address: ori.avinoam@weizmann.ac.il.
Weizmann Institute of Science · ILBen-Gurion University of the Negev · ILCincinnati Children's Hospital Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myoblast fusion is essential for muscle development and regeneration. Yet, it remains poorly understood how mononucleated myoblasts fuse with preexisting fibers. We demonstrate that ERK1/2 inhibition (ERKi) induces robust differentiation and fusion of primary mouse myoblasts through a linear pathway involving RXR, ryanodine receptors, and calcium-dependent activation of CaMKII in nascent myotubes. CaMKII activation results in myotube growth via fusion with mononucleated myoblasts at a fusogenic synapse. Mechanistically, CaMKII interacts with and regulates MYMK and Rac1, and CaMKIIδ/γ knockout mice exhibit smaller regenerated myofibers following injury. In addition, the expression of a dominant negative CaMKII inhibits the formation of large multinucleated myotubes. Finally, we demonstrate the evolutionary conservation of the pathway in chicken myoblasts. We conclude that ERK1/2 represses a signaling cascade leading to CaMKII-mediated fusion of myoblasts to myotubes, providing an attractive target for the cultivated meat industry and regenerative medicine.

Indexed as

ActinsAnimalsCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell DifferentiationCell FusionCell ProliferationEnzyme ActivationExtracellular Signal-Regulated MAP KinasesMiceMice, Inbred C57BLModels, BiologicalMuscle Fibers, SkeletalMuscle ProteinsMyoblastsProtein BindingActinsCalciumCalcium-Calmodulin-Dependent Protein Kinase Type 2Extracellular Signal-Regulated MAP KinasesMuscle ProteinsProtein Kinase Inhibitorsrac1 GTP-Binding ProteinReceptors, Retinoic AcidcalciumCaMKIIcultivated meatERK1/2muscle regenerationmyoblast fusionmyogenesis

Identifiers

PMID34932950
PMCPMC8693863
OpenAlexW4200612966

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.