Filamin C regulates skeletal muscle atrophy by stabilizing dishevelled-2 to inhibit autophagy and mitophagy

Molecular Therapy: Nucleic Acids

卷:27

Huadong Yin¹  Yun Zhang²  Menggen Ma³  Yao Zhang⁴  Jing Zhao⁴  Can Cui⁴  Xiyu Zhao⁴  Qing Zhu⁴  Xiaoxu Shen⁴  Haorong He⁴  Diyan Li⁴  Shunshun Han⁴  Jianping Wang⁵ 

[1] Corresponding author: Qing Zhu, Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.;

[2] College of Management, Sichuan Agricultural University, Chengdu, Sichuan 611130, China;

[3] College of Resources, Sichuan Agricultural University, Chengdu, Sichuan 611130, China;

[4] Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, China;

[5] Key Laboratory for Animal Disease Resistance Nutrition of China, Institute of Animal Nutrition, Ministry of Education, Sichuan Agricultural University, Chengdu, Sichuan 611130, China;

关键词: filamin C;    skeletal muscle;    atrophy;    dishevelled-2;    autophagy;    mitophagy;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 in vitro and in vivo 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 vivo 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.

【 授权许可】

Unknown