Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth.
Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth.
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DOI：
10.1002/jcp.25294
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发表时间：
2016-09
影响因子：
5.6
通讯作者：
McCarthy JJ
中科院分区：
文献类型：
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作者：
Chaillou T;Zhang X;McCarthy JJ
核糖体历来被认为没有细胞特有的功能，而是起到“看家”的作用。有证据表明，核糖体蛋白质组成的异质性可以导致核糖体的功能特化，这一观点受到了挑战。不同组织的表达谱显示，核糖体蛋白Large-3-like(Rpl3l)仅在横纹肌中表达。在肥大刺激下，Rpl3l在骨骼肌中的表达显著降低82%，而普遍存在的Paralog Rpl3的表达显著增加~5倍。基于这些发现，我们提出了Rpl3l作为肌肉生长的负调节因子的假设。为了验证这一假设，我们使用Tet-on系统在肌管形成期间的成肌细胞中表达Rpl3l。为了支持我们的假设，根据肌管直径(−23%)和蛋白质含量(−14%)评估，RPL3L表达显著损害肌管生长。进一步分析表明，这种损害的基础是成肌细胞融合指数显着降低(−17%)，并伴随着RPL3L的表达。这些发现是支持骨骼肌核糖体特化的新概念及其在骨骼肌生长调节中的作用的第一个证据。
The ribosome has historically been considered to have no cell-specific function but rather serve in a “housekeeping” capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ~5-fold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (−23%) and protein content (−14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (−17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth.