Folker Eric S, Baylies Mary K
Department of Biology, Boston College Chestnut Hill, MA, USA.
Department of Developmental Biology, Sloan-Kettering Institute New York, NY, USA.
Front Physiol. 2013 Dec 12;4:363. doi: 10.3389/fphys.2013.00363.
Muscle disease as a group is characterized by muscle weakness, muscle loss, and impaired muscle function. Although the phenotype is the same, the underlying cellular pathologies, and the molecular causes of these pathologies, are diverse. One common feature of many muscle disorders is the mispositioning of myonuclei. In unaffected individuals, myonuclei are spaced throughout the periphery of the muscle fiber such that the distance between nuclei is maximized. However, in diseased muscles, the nuclei are often clustered within the center of the muscle cell. Although this phenotype has been acknowledged for several decades, it is often ignored as a contributor to muscle weakness. Rather, these nuclei are taken only as a sign of muscle repair. Here we review the evidence that mispositioned myonuclei are not merely a symptom of muscle disease but also a cause. Additionally, we review the working models for how myonuclei move from two different perspectives: from that of the nuclei and from that of the cytoskeleton. We further compare and contrast these mechanisms with the mechanisms of nuclear movement in other cell types both to draw general themes for nuclear movement and to identify muscle-specific considerations. Finally, we focus on factors that can be linked to muscle disease and find that genes that regulate myonuclear movement and positioning have been linked to muscular dystrophy. Although the cause-effect relationship is largely speculative, recent data indicate that the position of nuclei should no longer be considered only a means to diagnose muscle disease.
肌肉疾病作为一个群体，其特征是肌肉无力、肌肉萎缩和肌肉功能受损。尽管表型相同，但其潜在的细胞病理学以及这些病理学的分子原因却多种多样。许多肌肉疾病的一个共同特征是肌细胞核位置异常。在未受影响的个体中，肌细胞核分布在肌纤维的整个周边，以使细胞核之间的距离最大化。然而，在患病肌肉中，细胞核常常聚集在肌细胞的中心。尽管这种表型已被认识数十年，但它作为肌肉无力的一个促成因素却常常被忽视。相反，这些细胞核仅被视为肌肉修复的一个标志。在此，我们综述相关证据，表明位置异常的肌细胞核不仅是肌肉疾病的一个症状，也是一个病因。此外，我们从细胞核和细胞骨架这两个不同视角综述肌细胞核移动的工作模型。我们进一步将这些机制与其他细胞类型中细胞核移动的机制进行比较和对比，以得出细胞核移动的一般规律，并确定肌肉特有的考量因素。最后，我们聚焦于可与肌肉疾病相关联的因素，发现调节肌细胞核移动和定位的基因已与肌肉营养不良相关联。尽管因果关系大多是推测性的，但最近的数据表明，细胞核的位置不应再仅被视为诊断肌肉疾病的一种手段。
