The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy.
Animals
Apoptosis
/ genetics
Autophagosomes
/ metabolism
Autophagy
/ genetics
Autophagy-Related Protein 5
/ genetics
Autophagy-Related Protein 7
/ genetics
Beclin-1
/ metabolism
Caspases
/ metabolism
Cells, Cultured
Chick Embryo
Chickens
Gene Expression Regulation
/ genetics
Gene Knockdown Techniques
Gene Ontology
Gene Silencing
LIM Domain Proteins
/ genetics
Microscopy, Electron, Transmission
Microtubule-Associated Proteins
/ genetics
Muscle Development
/ genetics
Muscle Fibers, Skeletal
/ cytology
Muscle Proteins
/ genetics
Muscle, Skeletal
/ metabolism
Muscular Dystrophies
/ genetics
Myoblasts
/ metabolism
RNA, Small Interfering
RNA-Seq
CSRP3
apoptosis
atrophy
autophagy
myoblasts
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
23 Jan 2020
23 Jan 2020
Historique:
received:
22
12
2019
revised:
17
01
2020
accepted:
20
01
2020
entrez:
26
1
2020
pubmed:
26
1
2020
medline:
18
11
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31979369
pii: ijms21030749
doi: 10.3390/ijms21030749
pmc: PMC7037376
pii:
doi:
Substances chimiques
Autophagy-Related Protein 5
0
Beclin-1
0
LIM Domain Proteins
0
Microtubule-Associated Proteins
0
Muscle Proteins
0
RNA, Small Interfering
0
cysteine and glycine-rich protein 3
0
Caspases
EC 3.4.22.-
Autophagy-Related Protein 7
EC 6.2.1.45
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : China Agriculture Research System
ID : CARS-40
Organisme : Sichuan Science and Technology Program
ID : 2016NYZ0050
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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