Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy.
Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy.
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DOI：
10.1083/jcb.201110067
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发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
Goldberg AL
中科院分区：
文献类型：
--
作者：
Cohen S;Zhai B;Gygi SP;Goldberg AL
在禁食诱导的肌肉萎缩期间，Trim 32促进结蛋白细胞骨架的降解，这与Z带和细丝的丢失有关。在肌肉萎缩期间，肌原纤维蛋白在有序过程中降解，其中MuRF 1催化粗丝组分的泛素化（Cohen等人，2009. http：//dx.doi.org/10.1083/jcb.200901052）。在这里，我们发现另一种泛素连接酶Trim 32使细丝（肌动蛋白、原肌球蛋白、肌钙蛋白）和Z带（α-辅肌动蛋白）组分泛素化，并促进它们的降解。在禁食期间下调Trim 32减少了纤维萎缩和细丝的快速损失。提出了结蛋白丝以保持细丝的完整性。因此，我们发现，快速破坏的细丝蛋白禁食时，伴随着增加磷酸化的结蛋白丝，这促进了结蛋白泛素化的Trim 32和降解。降低Trim 32水平防止了结蛋白和细丝蛋白的损失。此外，结蛋白聚合抑制剂的过度表达会诱导结蛋白丝的分解和细丝成分的破坏。因此，在禁食期间，结蛋白磷酸化增加并增强Trim 32介导的结蛋白细胞骨架降解，这似乎有助于Z带和细丝的分解。
During muscle atrophy induced by fasting, Trim32 promotes degradation of desmin cytoskeleton, which is linked to the loss of Z-bands and thin filaments. 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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DOI：
10.1073/pnas.0600158103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Chiang, AP;Beck, JS;Sheffield, VC
通讯作者：
Sheffield, VC
影响因子：
4.7
作者：
Horn, EJ;Albor, A;Kulesz-Martin, M
通讯作者：
Kulesz-Martin, M
DOI：
10.1083/jcb.200901052
发表时间：
2009-06-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cohen S;Brault JJ;Gygi SP;Glass DJ;Valenzuela DM;Gartner C;Latres E;Goldberg AL
通讯作者：
Goldberg AL
影响因子：
29
作者：
Clarke, Brian A.;Drujan, Doreen;Glass, David J.
通讯作者：
Glass, David J.
影响因子：
4.8
作者：
Chen, F;Chang, R;Cryns, VL
通讯作者：
Cryns, VL