Han Shunshun, Cui Can, Zhao Xiyu, Zhang Yao, Zhang Yun, Zhao Jing, Shen Xiaoxu, He Haorong, Wang Jianping, Ma Menggen, Li Diyan, Zhu Qing, Yin Huadong
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
College of Management, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
Mol Ther Nucleic Acids. 2021 Nov 29;27:147-164. doi: 10.1016/j.omtn.2021.11.022. eCollection 2022 Mar 8.
FilaminC (Flnc) is a member of the actin binding protein family, which is preferentially expressed in the cardiac and skeletal muscle tissues. Although it is known to interact with proteins associated with myofibrillar myopathy, its unique role in skeletal muscle remains largely unknown. In this study, we identify the biological functions of Flnc and using chicken primary myoblast cells and animal models, respectively. From the results, we observe that the growth rate and mass of the skeletal muscle of fast-growing chickens (broilers) were significantly higher than those in slow-growing chickens (layers). Furthermore, we find that the expression of Flnc in the skeletal muscle of broilers was higher than that in the layers. Our results indicated that Flnc was highly expressed in the skeletal muscle, especially in the skeletal muscle of broilers than in layers. This suggests that Flnc plays a positive regulatory role in myoblast development. Flnc knockdown resulted in muscle atrophy, whereas the overexpression of Flnc promotes muscle hypertrophy in an animal model. We also found that Flnc interacted with dishevelled-2 (Dvl2), activated the wnt/β-catenin signaling pathway, and controlled skeletal muscle development. Flnc also antagonized the LC3-mediated autophagy system by decreasing Dvl2 ubiquitination. Moreover, Flnc knockdown activated and significantly increased mitophagy. In summary, these results indicate that the absence of Flnc induces autophagy or mitophagy and regulates muscle atrophy.
细丝蛋白C（Flnc）是肌动蛋白结合蛋白家族的成员，在心脏和骨骼肌组织中优先表达。尽管已知它能与与肌原纤维肌病相关的蛋白质相互作用，但其在骨骼肌中的独特作用仍 largely 未知。在本研究中，我们分别使用鸡原代成肌细胞和动物模型来确定 Flnc 的生物学功能。从结果来看，我们观察到快速生长鸡（肉鸡）的骨骼肌生长速率和质量显著高于慢速生长鸡（蛋鸡）。此外，我们发现肉鸡骨骼肌中 Flnc 的表达高于蛋鸡。我们的结果表明，Flnc 在骨骼肌中高表达，尤其是在肉鸡骨骼肌中比在蛋鸡中更高。这表明 Flnc 在成肌细胞发育中起正向调节作用。在动物模型中，Flnc 敲低导致肌肉萎缩，而 Flnc 的过表达促进肌肉肥大。我们还发现 Flnc 与散乱蛋白-2（Dvl2）相互作用，激活 wnt/β-连环蛋白信号通路，并控制骨骼肌发育。Flnc 还通过减少 Dvl2 泛素化来拮抗 LC3 介导的自噬系统。此外，Flnc 敲低激活并显著增加了线粒体自噬。总之，这些结果表明 Flnc 的缺失诱导自噬或线粒体自噬并调节肌肉萎缩。
