Cited by 205Muscle Physiology and DisordersUbiquitin and proteasome pathwaysMeat and Animal Product Quality

Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy

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Cohen, Shenhav, Zhai, Bo, Gygi, Steven P., Goldberg, Alfred L.·2012·Journal of Cell Biology

Abstract

During muscle atrophy, myofibrillar proteins are degraded in an ordered process in which MuRF1 catalyzes ubiquitylation of thick filament components (Cohen et al. 2009. J. Cell Biol. http://dx.doi.org/10.1083/jcb.200901052). Here, we show that another ubiquitin ligase, Trim32, ubiquitylates thin filament (actin, tropomyosin, troponins) and Z-band (α-actinin) components and promotes their degradation. Down-regulation of Trim32 during fasting reduced fiber atrophy and the rapid loss of thin filaments. Desmin filaments were proposed to maintain the integrity of thin filaments. Accordingly, we find that the rapid destruction of thin filament proteins upon fasting was accompanied by increased phosphorylation of desmin filaments, which promoted desmin ubiquitylation by Trim32 and degradation. Reducing Trim32 levels prevented the loss of both desmin and thin filament proteins. Furthermore, overexpression of an inhibitor of desmin polymerization induced disassembly of desmin filaments and destruction of thin filament components. Thus, during fasting, desmin phosphorylation increases and enhances Trim32-mediated degradation of the desmin cytoskeleton, which appears to facilitate the breakdown of Z-bands and thin filaments.

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Authors
Cohen, S., Zhai, B., Gygi, S. P., & Goldberg, A. L.
Affiliations
Harvard University (US)
Corresponding author
Goldberg, Alfred L.
Venue
Journal of Cell Biology
Published
2012-08-20
Volume
198
Issue
4
Pages
575-589
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2105555459
Cited by
205
References
54
Citations by year
2026: 11 · 2025: 9 · 2024: 14 · 2023: 9 · 2022: 12 · 2021: 21 · 2020: 19 · 2019: 11 · 2018: 16 · 2017: 11 · 2016: 11 · 2015: 23 · 2014: 20 · 2013: 16 · 2012: 1
FWCI
7.71
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
Keywords
TRIM32, ubiquitination, muscle atrophy, desmin, thin filament, Z-band, alpha-actinin, tropomyosin, troponin, actin, MuRF1, fasting, ubiquitin ligase, myofibrillar protein degradation
MeSH terms
Actins, Animals, Desmin, Fasting, Male, Mice, Inbred Strains, Actin Cytoskeleton, Muscular Atrophy, Myofibrils, Phosphorylation, Sarcomeres, Ubiquitin-Protein Ligases, Mice, Ubiquitination

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