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Comprehensive Analysis of the Proteome and PTMomes of C2C12 Myoblasts Reveals that Sialylation Plays a Role in the Differentiation of Skeletal Muscle Cells
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-11-20 , DOI: 10.1021/acs.jproteome.0c00353
Xiulan Chen 1, 2 , Yaping Sun 1, 2 , Tingting Zhang 1, 2 , Peter Roepstorff 3 , Fuquan Yang 1, 2
Affiliation  

The C2C12 myoblast is a model that has been used extensively to study the process of skeletal muscle differentiation. Proteomics has advanced our understanding of skeletal muscle biology and also the differentiation process of skeletal muscle cells. However, there is still no comprehensive analysis of C2C12 myoblast proteomes, which is important for the understanding of key drivers for the differentiation of skeletal muscle cells. Here, we conducted multidimensional proteome profiling to get a comprehensive analysis of proteomes and PTMomes of C2C12 myoblasts with a TiSH strategy. A total of 8313 protein groups were identified, including 7827 protein groups from nonmodified peptides, 3803 phosphoproteins, and 977 formerly sialylated N-linked glycoproteins. Integrated analysis of proteomic and PTMomic data showed that almost all of the kinases and transcription factors in the muscle cell differentiation pathway were phosphorylated. Further analysis indicated that sialylation might play a role in the differentiation of C2C12 myoblasts. Further functional analysis demonstrated that C2C12 myoblasts showed a decreased level of sialylation during skeletal muscle cell differentiation. Inhibition of sialylation with the sialyltransferase inhibitor 3Fax-Neu5Ac resulted in the lower expression of MHC and suppression of myoblast fusion. In all, these results indicate that sialylation has an effect on the differentiation of skeletal muscle cells.

中文翻译:

C2C12成肌细胞的蛋白质组和PTMome的综合分析表明唾液酸化在骨骼肌细胞的分化中发挥作用

C2C12成肌细胞是一种已广泛用于研究骨骼肌分化过程的模型。蛋白质组学提高了我们对骨骼肌生物学以及骨骼肌细胞分化过程的理解。但是,仍没有对C2C12成肌细胞蛋白质组的全面分析,这对于理解骨骼肌细胞分化的关键驱动因素很重要。在这里,我们进行了多维蛋白质组分析,以TiSH策略对C2C12成肌细胞的蛋白质组和PTMome进行了全面分析。总共鉴定出8313个蛋白质组,其中包括来自未修饰肽的7827个蛋白质组,3803个磷蛋白和977个以前被唾液酸化的N-连接糖蛋白。蛋白质组学和PTMomic数据的综合分析表明,肌肉细胞分化途径中的几乎所有激酶和转录因子都被磷酸化了。进一步的分析表明唾液酸化可能在C2C12成肌细胞的分化中起作用。进一步的功能分析表明,C2C12成肌细胞在骨骼肌细胞分化过程中唾液酸化水平降低。用唾液酸转移酶抑制剂3Fax-Neu5Ac抑制唾液酸化导致MHC表达降低和成肌细胞融合受到抑制。总之,这些结果表明唾液酸化对骨骼肌细胞的分化有影响。进一步的分析表明唾液酸化可能在C2C12成肌细胞的分化中起作用。进一步的功能分析表明,C2C12成肌细胞在骨骼肌细胞分化过程中唾液酸化水平降低。用唾液酸转移酶抑制剂3Fax-Neu5Ac抑制唾液酸化导致MHC表达降低和成肌细胞融合受到抑制。总之,这些结果表明唾液酸化对骨骼肌细胞的分化有影响。进一步的分析表明唾液酸化可能在C2C12成肌细胞的分化中起作用。进一步的功能分析表明,C2C12成肌细胞在骨骼肌细胞分化过程中唾液酸化水平降低。用唾液酸转移酶抑制剂3Fax-Neu5Ac抑制唾液酸化导致MHC表达降低和成肌细胞融合受到抑制。总之,这些结果表明唾液酸化对骨骼肌细胞的分化有影响。
更新日期:2021-01-01
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