Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy
Open accessAbstract
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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Trim32 controls the thin filaments (actin, tropomyosin, troponins), the Z-band protein α-actinin, and desmin.
“Trim32 has been found to control the thin filaments (actin, tropomyosin, troponins), the Z-band protein α-actinin, and desmin47.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [47]
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1 retracted
Lokireddy, S., McFarlane, C., Ge, X., Zhang, H., Sze, S. K., Sharma, M., & Kambadur, R. (2011) · Molecular Endocrinology · doi:10.1210/me.2011-1124 · Cited by 116 · see citing works
RetractedIdentification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521 · see citing works
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012 · see citing works
Self-citationFoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953 · see citing works
Self-citationAtrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251541198 · Cited by 1,774 · see citing works
Self-citationMultiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539 · see citing works
Self-citationZhao, J., Brault, J. J., Schild, A., Cao, P., Sandri, M., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.004 · Cited by 1,489 · see citing works
Self-citationProtein degradation by the ubiquitin-proteasome pathway in normal and disease states
Lecker, S. H., Goldberg, A. L., & Mitch, W. E. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006010083 · Cited by 1,234 · see citing works
Self-citationThe Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase
Joazeiro, C. A. P., Wing, S. S., Huang, H.-K., Leverson, J. D., Hunter, T. R., & Liu, Y. (1999) · Science · doi:10.1126/science.286.5438.309 · Cited by 1,036 · see citing works
The Molecular Basis of Skeletal Muscle Atrophy
Jackman, R. W., & Kandarian, S. C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00579.2003 · Cited by 1,008 · see citing works
Du, J., Wang, X., Miereles, C., Bailey, J. L., Debigaré, R., Zheng, B., Price, S. R., & Mitch, W. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18330 · Cited by 730 · see citing works
The E3 Ligase MuRF1 Degrades Myosin Heavy Chain Protein in Dexamethasone-Treated Skeletal Muscle
Clarke, B. A., Drujan, D., Willis, M. S., Murphy, L. O., Corpina, R. A., Burova, E., Rakhilin, S. V., Stitt, T. N., Patterson, C., Latres, E., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.009 · Cited by 683 · see citing works
Sacheck, J. M., Hyatt, J. K., Raffaello, A., Thomas Jagoe, R., Roy, R. R., Reggie Edgerton, V., Lecker, S. H., & Goldberg, A. L. (2007) · The FASEB Journal · doi:10.1096/fj.06-6604com · Cited by 585 · see citing works
Self-citationCohen, S., Brault, J. J., Gygi, S. P., Glass, D. J., Valenzuela, D. M., Gartner, C. A., Latres, E., & Goldberg, A. L. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200901052 · Cited by 584 · see citing works
Self-citationRabinovich, E., Kerem, A., Fröhlich, K., Diamant, N., & Bar‐Nun, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.2.626-634.2002 · Cited by 546 · see citing works
Disruption of muscle architecture and myocardial degeneration in mice lacking desmin.
Milner, D. J., Weitzer, G., Tran, D., Bradley, A., & Capetanaki, Y. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.134.5.1255 · Cited by 522 · see citing works
Site-specific phosphorylation induces disassembly of vimentin filaments in vitro
Inagaki, M., Nishi, Y., Nishizawa, K., Matsuyama, M., & Sato, C. (1987) · Nature · doi:10.1038/328649a0 · Cited by 440 · see citing works
Chiang, A. P.-F., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K. A., Huang, J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600158103 · Cited by 433 · see citing works
Solomon, V., & Goldberg, A. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.26690 · Cited by 432 · see citing works
Self-citationGeisler, N., & Weber, K. (1982) · The EMBO Journal · doi:10.1002/j.1460-2075.1982.tb01368.x · Cited by 430 · see citing works
Immunological characterization of the subunit of the 100 A filaments from muscle cells.
Lazarides, E., & Hubbard, B. D. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.12.4344 · Cited by 429 · see citing works
Li, Z., Mericskay, M., Agbulut, O., Butler-Browne, G. S., Carlsson, L. M. S., Thornell, L., Babinet, C., & Paulin, D. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.1.129 · Cited by 362 · see citing works
Effects of food deprivation on protein synthesis and degradation in rat skeletal muscles
Li, J., & Goldberg, A. (1976) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1976.231.2.441 · Cited by 288 · see citing works
Self-citationMyosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3
Fielitz, J., Kim, M.-S., Shelton, J. M., Latif, S., Spencer, J. A., Glass, D. J., Richardson, J. A., Bassel‐Duby, R., & Olson, E. N. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32827 · Cited by 271 · see citing works
Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., & Wrogemann, K. (2002) · The American Journal of Human Genetics · doi:10.1086/339083 · Cited by 261 · cited 3× · see citing works
“In humans, mutations at the third NHL repeat cause limb girdle muscular dystrophy 2H (Frosk et al., 2002), but the effects of these mutations on its function are unclear.”
BackgroundInfluentialGeisler, N., & Weber, K. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb02778.x · Cited by 223 · see citing works
Brault, J. J., Jespersen, J. G., & Goldberg, A. L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.113092 · Cited by 217 · see citing works
Self-citationTidball, J. G., & Spencer, M. J. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.024935 · Cited by 210 · see citing works
Kudryashova, E., Kudryashov, D. S., Kramerova, I. A., & Spencer, M. J. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.09.068 · Cited by 207 · see citing works
A Predictive Scale for Evaluating Cyclin-dependent Kinase Substrates
Holmes, J. K., & Solomon, M. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.41.25240 · Cited by 206 · see citing works
Kaufmann, E., Weber, K. K., & Geisler, N. (1985) · Journal of Molecular Biology · doi:10.1016/0022-2836(85)90058-0 · Cited by 196 · see citing works
Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor
Zhao, J., Brault, J. J., Schild, A., & Goldberg, A. L. (2008) · Autophagy · doi:10.4161/auto.5633 · Cited by 164 · see citing works
Self-citationA novel repeat domain that is often associated with RING finger and B-box motifs
Slack, F. J., & Ruvkun, G. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01299-7 · Cited by 151 · see citing works
TRIM32 is an E3 ubiquitin ligase for dysbindin
Locke, M., Tinsley, C. L., Benson, M. A., & Blake, D. J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp167 · Cited by 147 · see citing works
Kano, S., Miyajima, N., Fukuda, S., & Hatakeyama, S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6231 · Cited by 127 · see citing works
Horn, E. J. (2003) · Carcinogenesis · doi:10.1093/carcin/bgh003 · Cited by 126 · see citing works
Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component
Kudryashova, E., Wu, J., Havton, L. A., & Spencer, M. J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp036 · Cited by 117 · see citing works
Desmin mutations as a cause of right ventricular heart failure affect the intercalated disks
Otten, E., Asimaki, A., Maass, A. H., van Langen, I. M., van der Wal, A. C., de Jonge, N., van den Berg, M. P., Saffitz, J. E., Wilde, A. A. M., Jongbloed, J. D. H., et al. (2010) · Heart Rhythm · doi:10.1016/j.hrthm.2010.04.023 · Cited by 112 · see citing works
The distribution of desmin (100 Å) filaments in primary cultures of embryonic chick cardiac cells
Lazarides, E. (1978) · Experimental Cell Research · doi:10.1016/0014-4827(78)90209-4 · Cited by 110 · see citing works
Kawajiri, A., Yasui, Y., Goto, H., Tatsuka, M., Takahashi, M., Nagata, K., & Inagaki, M. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-09-0612 · Cited by 108 · see citing works
Chen, F., Chang, R., Trivedi, M., Capetanaki, Y., & Cryns, V. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212021200 · Cited by 104 · see citing works
加納, 里. (2009) · Medical Entomology and Zoology · Cited by 96 · see citing works
Absence of caspase-3 protects against denervation-induced skeletal muscle atrophy
Plant, P. J., Bain, J. R., Correa, J., Woo, M., & Batt, J. A. E. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90932.2008 · Cited by 90 · see citing works
Brain site‐specific gene expression analysis in Alzheimer's disease patients
Yokota, T., Mishra, M., Akatsu, H., Tani, Y., Miyauchi, T., Yamamoto, T., Kosaka, K., Nagai, Y., Sawada, T., & Heese, K. (2006) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2006.01722.x · Cited by 85 · see citing works
Regulation of the Psoriatic Chemokine CCL20 by E3 Ligases Trim32 and Piasy in Keratinocytes
Liu, Y., Lagowski, J. P., Gao, S., Raymond, J. H., White, C. R., & Kulesz-Martin, M. F. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.416 · Cited by 62 · see citing works
Fast-to-slow transformation in stimulated rat muscle
Jarvis, J. C., Mokrusch, T., Kwende, M. M. N., Sutherland, H., & Salmons, S. (1996) · Muscle & Nerve · doi:10.1002/(sici)1097-4598(199611)19:11 · Cited by 60 · see citing works
A Myopathy-linked Desmin Mutation Perturbs Striated Muscle Actin Filament Architecture
Conover, G. M., Henderson, S. N., & Gregorio, C. C. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-07-0753 · Cited by 60 · see citing works
Neti, G., Novak, S. M., Thompson, V. F., & Goll, D. E. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00022.2009 · Cited by 51 · see citing works
Kudryashova, E., Struyk, A. F., Mokhonova, E. I., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr311 · Cited by 46 · see citing works
Huang, X., Li, J., Foster, D., et al. (2002) · Experimental Biology and Medicine · doi:10.1177/153537020222701113 · Cited by 42 · see citing works
Helliwell, T. R., Günhan, Ö., & Edwards, R. H. T. (1989) · The Journal of Pathology · doi:10.1002/path.1711590111 · Cited by 37 · see citing works
Wyke, S. M., & Tisdale, M. J. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.11.014 · Cited by 35 · see citing works
Inagaki, N., Tsujimura, K., Tanaka, J., Sekimata, M., Kamei, Y., & Inagaki, M. (1996) · Neurochemical Research · doi:10.1007/bf02532302 · Cited by 25 · see citing works
The association of desmin with the developing myofibrils of cultured embryonic rat heart myocytes
Fuseler, J. W., & Shay, J. W. (1982) · Developmental Biology · doi:10.1016/0012-1606(82)90051-3 · Cited by 23 · see citing works
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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
- Publisher
- Rockefeller University Press
- Published
- 2012-08-20
- Volume
- 198
- Issue
- 4
- Pages
- 575-589
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3514026
- 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
- hybrid
- doi.org
- 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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