The MTM1–UBQLN2–HSP Complex Mediates Degradation of Misfolded Intermediate Filaments in Skeletal Muscle
Abstract
The ubiquitin proteasome system and autophagy are major protein turnover mechanisms in muscle cells, which ensure stemness and muscle fibre maintenance. Muscle cells contain a high proportion of cytoskeletal proteins, which are prone to misfolding and aggregation; pathological processes that are observed in several neuromuscular diseases called proteinopathies. Despite advances in deciphering the mechanisms underlying misfolding and aggregation, little is known about how muscle cells manage cytoskeletal degradation. Here, we describe a process by which muscle cells degrade the misfolded intermediate filament proteins desmin and vimentin by the proteasome. This relies on the MTM1-UBQLN2 complex to recognize and guide these misfolded proteins to the proteasome and occurs prior to aggregate formation. Thus, our data highlight a safeguarding function of the MTM1-UBQLN2 complex that ensures cytoskeletal integrity to avoid proteotoxic aggregate formation.
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The ubiquitin-proteasome system plays a major role in protein content turnover by degrading misfolded or defective proteins.
“The ubiquitin–proteasome system plays a major role in protein content turnover by degrading misfolded or defective proteins [163,164].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [164]
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Background
- Authors
- Gavriilidis, C., Laredj, L., Solinhac, R., Messaddeq, N., Viaud, J., Laporte, J., Sumara, I., & Hnia, K.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Hnia, Karim
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2018-01-22
- Volume
- 20
- Issue
- 2
- Pages
- 198-210
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2792552001
- Cited by
- 56
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 2 · 2022: 8 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 6
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-IDEX-0002, ANR-10-LABX-0030)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- MTM1, UBQLN2, desmin, vimentin, intermediate filaments, protein misfolding, protein aggregation, ubiquitin-proteasome system, proteasomal degradation, skeletal muscle, cytoskeletal integrity, proteinopathies, proteotoxicity, autophagy
- MeSH terms
- Autophagy-Related Proteins, Autophagy, Cytoskeleton, Desmin, Humans, Intermediate Filament Proteins, Ubiquitins, Vimentin, Protein Folding, Muscle, Skeletal, Cell Cycle Proteins, Ubiquitin, Proteasome Endopeptidase Complex, Adaptor Proteins, Signal Transducing, Protein Tyrosine Phosphatases, Non-Receptor, Proteolysis, Protein Aggregates
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