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Smyd1a在骨骼肌肌原纤维组织中的表达及功能特性

Expression and functional characterization of Smyd1a in myofibril organization of skeletal muscles.

作者信息

Gao Jie, Li Junling, Li Bao-Jun, Yagil Ezra, Zhang Jianshe, Du Shao Jun

机构信息

Institute of Marine and Environmental Technology, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangdong, China.

Institute of Marine and Environmental Technology, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

出版信息

PLoS One. 2014 Jan 23;9(1):e86808. doi: 10.1371/journal.pone.0086808. eCollection 2014.

Abstract

BACKGROUND

Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown.

METHODOLOGY/PRINCIPAL FINDINGS: To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos.

CONCLUSION/SIGNIFICANCE: Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process.

摘要

背景

Smyd1是Smyd家族(包括Smyd-1、2、3、4和5)的首个成员,是一种含有SET和MYND结构域的蛋白质,在骨骼肌和心肌的肌原纤维组装中起关键作用。生物信息学分析表明,斑马鱼基因组包含两个高度相关的smyd1基因,即smyd1a和smyd1b。尽管Smyd1b在骨骼肌和心肌中的功能已得到充分表征,但Smyd1a的功能尚不清楚。

方法/主要发现:为了研究Smyd1a在肌肉发育中的功能,我们从斑马鱼中分离出smyd1a,并通过基因敲低和转基因表达方法来表征其在肌肉发育过程中的表达和功能。结果表明,smyd1a在斑马鱼胚胎的骨骼肌中强烈表达。功能分析显示,单独敲低smyd1a对斑马鱼骨骼肌的肌原纤维组装没有显著影响。然而,同时敲低smyd1a和smyd1b会导致骨骼肌中肌原纤维组织的完全破坏,该表型比单独敲低smyd1a或smyd1b更强。此外,斑马鱼smyd1a或小鼠Smyd1转基因的异位表达可以挽救斑马鱼胚胎中smyd1b敲低导致的肌原纤维缺陷。

结论/意义:总体而言,这些数据表明Smyd1a和Smyd1b在斑马鱼胚胎的肌原纤维组装中具有相似的生物学活性。然而,Smyd1b似乎在这个过程中起主要作用。

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