Deletion of Pofut1 in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in cis and in trans
Open accessAbstract
Sarcopenia, the loss of muscle mass and strength during normal aging, involves coordinate changes in skeletal myofibers and the cells that contact them, including satellite cells and motor neurons. Here we show that the protein O-fucosyltransferase 1 gene (Pofut1), which encodes a glycosyltransferase required for NotchR-mediated cell-cell signaling, has reduced expression in aging skeletal muscle. Moreover, premature postnatal deletion of Pofut1 in skeletal myofibers can induce aging-related phenotypes in cis within skeletal myofibers and in trans within satellite cells and within motor neurons via the neuromuscular junction. Changed phenotypes include reduced skeletal muscle size and strength, decreased myofiber size, increased slow fiber (type 1) density, increased muscle degeneration and regeneration in aged muscles, decreased satellite cell self-renewal and regenerative potential, and increased neuromuscular fragmentation and occasional denervation. Pofut1 deletion in skeletal myofibers reduced NotchR signaling in young adult muscles, but this effect was lost with age. Increasing muscle NotchR signaling also reduced muscle size. Gene expression studies point to regulation of cell cycle genes, muscle myosins, NotchR and Wnt pathway genes, and connective tissue growth factor by Pofut1 in skeletal muscle, with additional effects on α dystroglycan glycosylation.
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Deletion of collagen VI or laminin-α1 (ECM components) or myofiber-specific deletion of O-fucosyltransferase 1 gene (Pofut1) impairs the self-renewal of SCs, leading to the shrinkage of the SC pool after multiple muscle injuries.
“Deletion of collagen VI or laminin-α1 (ECM components) or myofiber-specific deletion of O-fucosyltransferase 1 gene (Pofut1) impairs the self-renewal of SCs36–38, leading to the shrinkage of the SC pool after multiple muscle injuries.”
From In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche (2021) · cites this paper as [38]
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- Authors
- Zygmunt, D. A., Singhal, N., Kim, M.-L., Cramer, M. L., Crowe, K. E., Xu, R., Jia, Y., Adair, J., Martinez-Pena y Valenzuela, I., Akaaboune, M., White, P., Janssen, P. M., & Martin, P. T.
- Affiliations
- Nationwide Children's Hospital (US)
- Department of Molecular, Cellular and Developmental Biology, University of Michigan
- University of Michigan (US)
- Department of Physiology and Cell Biology, The Ohio State University
- Corresponding author
- Martin, Paul T.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2017-05-01
- Volume
- 37
- Issue
- 10
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC5477548
- OpenAlex
- W2591688689
- Cited by
- 15
- References
- 94
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (R01 AR049722)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- POFUT1, sarcopenia, muscle aging, satellite cells, motor neurons, neuromuscular junction, muscle degeneration and regeneration, muscle fiber size, connective tissue growth factor, alpha-dystroglycan glycosylation, Wnt signaling, cell cycle genes, muscle denervation
- MeSH terms
- Aging, Animals, Cells, Cultured, Female, Fucosyltransferases, Gene Expression Regulation, Male, Mice, Inbred C57BL, Motor Neurons, Neuromuscular Junction, Phenotype, Signal Transduction, Muscle Fibers, Skeletal, Cell Cycle Proteins, Gene Expression Profiling, Satellite Cells, Skeletal Muscle, Mice, Receptors, Notch, Sarcopenia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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