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Article

The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy

by
Can Cui
,
Shunshun Han
,
Shuyue Tang
,
Haorong He
,
Xiaoxu Shen
,
Jing Zhao
,
Yuqi Chen
,
Yuanhang Wei
,
Yan Wang
,
Qing Zhu
,
Diyan Li
and
Huadong Yin
*
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 749; https://doi.org/10.3390/ijms21030749
Submission received: 22 December 2019 / Revised: 17 January 2020 / Accepted: 20 January 2020 / Published: 23 January 2020
(This article belongs to the Special Issue Autophagy in Health, Ageing and Disease)
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Abstract

CSRP3/MLP (cysteine-rich protein 3/muscle Lim protein), a member of the cysteine-rich protein family, is a muscle-specific LIM-only factor specifically expressed in skeletal muscle. CSRP3 is critical in maintaining the structure and function of normal muscle. To investigate the mechanism of disease in CSRP3 myopathy, we performed siRNA-mediated CSRP3 knockdown in chicken primary myoblasts. CSRP3 silencing resulted in the down-regulation of the expression of myogenic genes and the up-regulation of atrophy-related gene expressions. We found that CSRP3 interacted with LC3 protein to promote the formation of autophagosomes during autophagy. CSRP3-silencing impaired myoblast autophagy, as evidenced by inhibited autophagy-related ATG5 and ATG7 mRNA expression levels, and inhibited LC3II and Beclin-1 protein accumulation. In addition, impaired autophagy in CSRP3-silenced cells resulted in increased sensitivity to apoptosis cell death. CSRP3-silenced cells also showed increased caspase-3 and caspase-9 cleavage. Moreover, apoptosis induced by CSRP3 silencing was alleviated after autophagy activation. Together, these results indicate that CSRP3 promotes the correct formation of autophagosomes through its interaction with LC3 protein, which has an important role in skeletal muscle remodeling and maintenance.
Keywords: CSRP3; myoblasts; autophagy; atrophy; apoptosis CSRP3; myoblasts; autophagy; atrophy; apoptosis

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MDPI and ACS Style

Cui, C.; Han, S.; Tang, S.; He, H.; Shen, X.; Zhao, J.; Chen, Y.; Wei, Y.; Wang, Y.; Zhu, Q.; et al. The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy. Int. J. Mol. Sci. 2020, 21, 749. https://doi.org/10.3390/ijms21030749

AMA Style

Cui C, Han S, Tang S, He H, Shen X, Zhao J, Chen Y, Wei Y, Wang Y, Zhu Q, et al. The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy. International Journal of Molecular Sciences. 2020; 21(3):749. https://doi.org/10.3390/ijms21030749

Chicago/Turabian Style

Cui, Can, Shunshun Han, Shuyue Tang, Haorong He, Xiaoxu Shen, Jing Zhao, Yuqi Chen, Yuanhang Wei, Yan Wang, Qing Zhu, and et al. 2020. "The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy" International Journal of Molecular Sciences 21, no. 3: 749. https://doi.org/10.3390/ijms21030749

APA Style

Cui, C., Han, S., Tang, S., He, H., Shen, X., Zhao, J., Chen, Y., Wei, Y., Wang, Y., Zhu, Q., Li, D., & Yin, H. (2020). The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy. International Journal of Molecular Sciences, 21(3), 749. https://doi.org/10.3390/ijms21030749

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