ArticleProceedings of the National Academy of Sciences of the United States of America2022
Phosphatidylserine orchestrates Myomerger membrane insertions to drive myoblast fusion.
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.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Mitochondrial Transport in Bone Metabolism Homeostasis: Molecular Mechanisms and Targeted Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Picalm coordinates clathrin-mediated endocytosis and actin remodeling during myogenesis.Molecular metabolism · 2026Article
- Myomerger-derived peptide enhances skeletal muscle tropism and reduces liver transduction of lipid nanoparticles for gene delivery.Molecular therapy. Nucleic acids · 2026Article
- Article
- CHAMP1 is an essential regulator for human myoblast fusion and muscle development.Nature communications · 2026Article
- Cell Surface Thiol Engineering Mechanoregulates Myogenic Differentiation via the FAK-PI3K-AKT Axis.Advanced healthcare materials · 2026Article
- Dynamic expression and differential requirement of the myocyte fusogen Myomixer during distinct myogenic episodes in the zebrafish.Biology open · 2025Article
- Bi-allelic MYMX variants cause a syndromic congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism.European journal of human genetics : EJHG · 2025Article
- Ectopic expression of Myomaker and Myomixer in slow muscle cells induces slow muscle fusion and myofiber death.Journal of genetics and genomics = Yi chuan xue bao · 2024Article
- Review
- Article
- Dietary "Beigeing" Fat Contains More Phosphatidylserine and Enhances Mitochondrial Function while Counteracting Obesity.Research (Washington, D.C.) · 2024Article
- Molecular regulation of myocyte fusion.Current topics in developmental biology · 2024Review
- Muscle Progenitor Cell Fusion in the Maintenance of Skeletal Muscle.Results and problems in cell differentiation · 2024Article
- Report and Abstracts of the 19th Meeting of the Interuniversity Institute of Myology: Assisi, October 20-23, 2022.European journal of translational myology · 2023Article
- Expression of Myomaker and Myomerger in myofibers causes muscle pathology.Skeletal muscle · 2023Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
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.
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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 Socratic graph.