Evidence map›Paper›PMID 36095199›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Phosphatidylserine orchestrates Myomerger membrane insertions to drive myoblast fusion.

Dilani G Gamage, Kamran Melikov, Paola Munoz-Tello, Tanner J Wherley, Leah C Focke, Evgenia Leikina, Elliana Huffman, Jiajie Diao, Douglas J Kojetin, Vikram Prasad and 2 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  13. Molecular regulation of myocyte fusion.Current topics in developmental biology · 2024
    Review
  14. Muscle Progenitor Cell Fusion in the Maintenance of Skeletal Muscle.Results and problems in cell differentiation · 2024
    Article
  15. Article
  16. 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

12 authors at 4 institutions in 1 country.

Dilani G GamageDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Kamran MelikovSection on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.
Paola Munoz-TelloDepartment of Integrative Structural and Computational Biology, University of Florida (UF) Scripps Biomedical Research, Jupiter, FL 33458.ORCID 0000-0002-5225-1907
Tanner J WherleyDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
Leah C FockeDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.ORCID 0000-0002-6560-2569
Evgenia LeikinaSection on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.
Elliana HuffmanSection on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.ORCID 0000-0002-9533-6230
Jiajie DiaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229.ORCID 0000-0003-4288-3203
Douglas J KojetinDepartment of Integrative Structural and Computational Biology, University of Florida (UF) Scripps Biomedical Research, Jupiter, FL 33458.ORCID 0000-0001-8058-6168
Vikram PrasadDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.ORCID 0000-0002-8852-3986
Leonid V ChernomordikSection on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892.
Douglas P MillayDivision of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.ORCID 0000-0001-5188-0720
Cincinnati Children's Hospital Medical Center · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USUniversity of Florida · USUniversity of Cincinnati Medical Center · US

Funding

Deciphering mechanisms of myoblast fusionR01AR068286 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI MILLAY, DOUGLAS PAUL · 2015 to 2024
$4.2M
Molecular basis of ligand activation of the orphan NR4A nuclear receptorsR01AG070719 · NIA · VANDERBILT UNIVERSITY · PI Douglas Kojetin · 2021 to 2026
$3.7M
The crosstalk of organelles involved in autophagosome biogenesisR35GM128837 · NIGMS · UNIVERSITY OF CINCINNATI · PI Jiajie Diao · 2018 to 2026
$3.3M
Role of skeletal muscle stem cell fusion and fibrosis during agingR01AG059605 · NIA · CINCINNATI CHILDRENS HOSP MED CTR · PI MILLAY, DOUGLAS PAUL · 2018 to 2022
$1.7M
Improving delivery of therapeutic material to skeletal muscleR61AR076771 · NIAMS · CINCINNATI CHILDRENS HOSP MED CTR · PI MILLAY, DOUGLAS PAUL · 2019 to 2020
$795k
NIAMS NIH HHS R01 AR068286NIAMS NIH HHS R61 AR076771NIA NIH HHS R01 AG059605NIA NIH HHS R01 AG070719NIGMS NIH HHS R35 GM128837
6 · The paper itself

Abstract

Muscle cell fusion is a multistep process where the final step of the reaction drives progression beyond early hemifusion events to complete fusion. This step requires activity of the muscle-specific fusogen Myomerger, a single-pass transmembrane protein containing 84 amino acids with an ectodomain that includes two α-helices. Previous studies have demonstrated that Myomerger acts by destabilizing membranes through generation of elastic stresses in the outer leaflet of the plasma membrane. An obvious question is how such destabilizing activity might be regulated to avoid membrane and cellular damage, and how the two juxtaposed helices cooperate in fusion. Using cellular fusion assays and in vitro liposome assays, we report that the two helices possess unique characteristics, both of which are needed for full activity of the protein. We demonstrate that externalized phosphatidylserine (PS), a lipid previously implicated in myoblast fusion, has a determinant role in the regulation of Myomerger activity. The membrane-proximal, amphipathic Helix-1 is normally disordered and its α-helical structure is induced by PS, making membrane interactions more efficacious. The distal, more hydrophobic Helix-2 is intrinsically ordered, possesses an ability to insert into membranes, and augments the membrane-stressing effects of Helix-1. These data reveal that Myomerger fusogenic activity is an exquisitely orchestrated event involving its two ectodomain helices, which are controlled by membrane lipid composition, providing an explanation as to how its membrane-stressing activity is spatially and temporally regulated during the final step of myoblast fusion.

Indexed as

Cell FusionMembrane ProteinsMyoblastsPhosphatidylserinesAnimalsCell LineHumansMiceMembrane ProteinsMYMX protein, humanPhosphatidylserinesmembrane fusionmyoblast fusionMyomerger/Myomixerphosphatidylserine

Identifiers

PMID36095199
PMCPMC9499509
OpenAlexW4295308898

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.