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For poultry breeding, muscle and fat are the two most concerned tissues in broiler production and sales
.
The poultry genetics and breeding team of the School of Animal Science of South China Agricultural University recently discovered that the TMEM182 gene plays a key role in both muscle production and fat deposition, which provides an important candidate target for breeding low-fat broilers
This article entitled "TMEM182 interacts with integrin beta 1 and regulates myoblast differentiation and muscle regeneration" was published in the "Journal of Cachexia, Sarcopenia and Muscle"
.
Associate Professor Luo Wen, a top-notch young talent in the Guangdong Special Support Program in science and technology innovation, is the first author of this article, and Professor Nie Qinghua, a leader in science and technology innovation in the National Special Support Program, and Professor Zhang Xiquan, the team leader, are the co-corresponding authors
As we all know, membrane proteins account for about 30% of the proteome and play a key role in many biological processes
.
Many of these processes involve muscle production, indicating that membrane proteins play an important role in muscles
In this study, the researchers used chickens and mice as animal models to identify TMEM182 in skeletal muscle
.
They found that TMEM182 is specifically expressed in muscle and adipose tissue and is directly regulated by MyoD1
TMEM182 is specifically expressed in muscle and adipose tissue
The researchers first found through in vitro analysis that the expression of TMEM182 gradually increased during the differentiation of chicken myoblasts and mouse myoblasts
.
In addition, TMEM182 is specifically expressed in muscle and adipose tissue of chickens, as well as mammals
Using dual luciferase reporter gene detection, they then explored the regulatory factors of TMEM182 transcription
.
They found that MyoD1, a transcription factor that regulates the expression of multiple muscle-related genes, can directly bind to the E-box on the TMEM182 promoter and induce its transcription during myoblast differentiation
TMEM182 inhibits muscle fiber formation and regeneration
In order to determine the function of TMEM182 in skeletal muscle cells, the researchers up-regulated and down-regulated TMEM182
.
They found that overexpression of TMEM182 inhibited myotube formation, while knockdown of TMEM182 had the opposite effect and promoted myotube formation
Considering that TMEM182 is a conserved gene shared by all vertebrates, the researchers then carried out studies using mice as a model to better understand the role of TMEM182 in muscle development
.
They commissioned Saiye to construct TMEM182 knockout (TMEM182-KO) mice
Figure 1.
TMEM182 knockout significantly increased muscle mass, muscle fiber number, and muscle fiber diameter
The analysis of mouse primary myoblasts also showed that knockout of TMEM182 significantly promoted the expression of myogenic marker genes, such as MyoG, MyHC and Myomaker
.
In addition, the knockout significantly increased the number of myotubes and the fusion rate of myoblasts, indicating that the knockout of TMEM182 promoted the differentiation of myoblasts
.
After muscle injury, knockout of TMEM182 also accelerated muscle regeneration
.
Compared with wild-type mice, muscle regeneration and repair in TMEM182-KO mice were completed earlier
.
The mechanism of TMEM182 inhibiting muscle production
In order to further understand the mechanism of TMEM182 inhibiting muscle production, they used co-immunoprecipitation and mass spectrometry to screen the proteins that bind to TMEM182
.
The analysis results show that there is a direct interaction between TMEM182 and integrin β1 (ITGB1)
.
Integrin β1 is a conserved cell surface receptor, involved in cell adhesion and muscle development, and has multiple domains
.
They found that this interaction requires the extracellular hybridization domain of integrin β1 (aa 387-470) and the conserved region in the extracellular macrocycle of TMEM182 (aa 52-62)
.
As an important component of extracellular matrix, laminin affects cell differentiation, migration and adhesion
.
Integrin β1 is a laminin receptor in skeletal muscle.
It interacts with laminin to regulate the differentiation, migration and adhesion of myoblasts
.
The researchers found that TMEM182 affected the interaction between integrin β1 and laminin, and inhibited the downstream signaling pathway mediated by integrin β1 (Figure 2)
.
Figure 2.
Schematic diagram of TMEM182 regulating muscle production and muscle regeneration
These results indicate that TMEM182 acts as a negative regulator in the process of muscle production, and inhibition of TMEM182 can accelerate muscle growth and regeneration
.
Interestingly, when the researchers compared the RNA-seq data of TMEM182-KO mice and wild-type mice, they also found that multiple enrichment pathways involve lipid metabolism.
Considering that TMEM182 is also specifically expressed in fat, it It may also play an important role in adipogenesis or fat deposition
.
The results of this research provide a framework for understanding the expression and regulation of TMEM182 in skeletal muscle, and provide an important candidate target for breeding low-fat broilers
.
Original text detection
Luo, W.
, Lin, Z.
, Chen, J.
, Chen, G.
, Zhang, S.
, Liu, M.
, Li, H.
, He, D.
, Liang, S.
, Luo, Q.
, Zhang, D.
, Nie, Q.
, and Zhang, X.
(2021) TMEM182 interacts with integrin beta 1 and regulates myoblast differentiation and muscle regeneration, Journal of Cachexia, Sarcopenia and Muscle, XXX, doi: https://doi.
org/10.
1002/jcsm.
12767