Cited by 1,022Muscle Physiology and DisordersMuscle and Compartmental DisordersCellular transport and secretion

Defective membrane repair in dysferlin-deficient muscular dystrophy

Bansal, Dimple, Miyake, Katsuya, Vogel, Steven S., Groh, Séverine, Chen, Chien-Chang, Williamson, Roger, McNeil, Paul L., Campbell, Kevin P.·2003·Nature

Abstract

Muscular dystrophy includes a diverse group of inherited muscle diseases characterized by wasting and weakness of skeletal muscle. Mutations in dysferlin are linked to two clinically distinct muscle diseases, limb-girdle muscular dystrophy type 2B and Miyoshi myopathy, but the mechanism that leads to muscle degeneration is unknown. Dysferlin is a homologue of the Caenorhabditis elegans fer-1 gene, which mediates vesicle fusion to the plasma membrane in spermatids. Here we show that dysferlin-null mice maintain a functional dystrophin-glycoprotein complex but nevertheless develop a progressive muscular dystrophy. In normal muscle, membrane patches enriched in dysferlin can be detected in response to sarcolemma injuries. In contrast, there are sub-sarcolemmal accumulations of vesicles in dysferlin-null muscle. Membrane repair assays with a two-photon laser-scanning microscope demonstrated that wild-type muscle fibres efficiently reseal their sarcolemma in the presence of Ca2+. Interestingly, dysferlin-deficient muscle fibres are defective in Ca2+-dependent sarcolemma resealing. Membrane repair is therefore an active process in skeletal muscle fibres, and dysferlin has an essential role in this process. Our findings show that disruption of the muscle membrane repair machinery is responsible for dysferlin-deficient muscle degeneration, and highlight the importance of this basic cellular mechanism of membrane resealing in human disease.

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Crossref · 10.1038/nature01573

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  • DYSF is implicated in membrane repair; ZNF638 mediates the silencing of unintegrated viral DNA.

    “DYSF is implicated in membrane repair22; ZNF638 mediates the silencing of unintegrated viral DNA23.”
  • DYSF functions mainly characterized in skeletal muscle where it participates in calcium-mediated membrane repair and regeneration.

    “Although widely expressed, its functions are mainly characterized in skeletal muscle where it participates in calcium-mediated membrane repair and regeneration22.”

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Authors
Bansal, D., Miyake, K., Vogel, S. S., Groh, S., Chen, C.-C., Williamson, R., McNeil, P. L., & Campbell, K. P.
Affiliations
  • University of Iowa (US)
  • Augusta University (US)
  • National Institutes of Health (US)
Corresponding author
Campbell, Kevin P.
Venue
Nature
Published
2003-05
Volume
423
Issue
6936
Pages
168-172
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2047136624
Cited by
1,022
References
27
Citations by year
2026: 22 · 2025: 35 · 2024: 47 · 2023: 35 · 2022: 53 · 2021: 42 · 2020: 64 · 2019: 41 · 2018: 36 · 2017: 38 · 2016: 56 · 2015: 55 · 2014: 55 · 2013: 48 · 2012: 51
FWCI
12.30
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Aeronautics and Space Administration
  • Muscular Dystrophy Association
  • National Institutes of Health
  • Roy J. and Lucille A. Carver College of Medicine, University of Iowa
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Surgery › Muscle and Compartmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
dysferlin, limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, membrane repair, dystrophin-glycoprotein complex, muscle degeneration
MeSH terms
Dysferlin, Animals, Calcium, Cell Membrane, Membrane Fusion, Membrane Proteins, Muscle Proteins, Muscular Dystrophies, Regeneration, Stress, Mechanical, Dystrophin, Gene Deletion, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Skeletal, Mice

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