School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, and.
Proteomics Facility, Centre of Excellence for Mass Spectrometry, King's College London, London, United Kingdom.
JCI Insight. 2018 Oct 4;3(19):120920. doi: 10.1172/jci.insight.120920.
Physiological and premature aging are frequently associated with an accumulation of prelamin A, a precursor of lamin A, in the nuclear envelope of various cell types. Here, we aimed to underpin the hitherto unknown mechanisms by which prelamin A alters myonuclear organization and muscle fiber function. By experimentally studying membrane-permeabilized myofibers from various transgenic mouse lines, our results indicate that, in the presence of prelamin A, the abundance of nuclei and myosin content is markedly reduced within muscle fibers. This leads to a concept by which the remaining myonuclei are very distant from each other and are pushed to function beyond their maximum cytoplasmic capacity, ultimately inducing muscle fiber weakness.
生理和过早衰老通常与核膜中各种细胞类型的前层粘连蛋白 A（lamin A 的前体）的积累有关。在这里，我们旨在阐明以前未知的前层粘连蛋白 A 改变肌核组织和肌肉纤维功能的机制。通过对来自各种转基因小鼠系的膜通透性肌纤维进行实验研究，我们的结果表明，在前层粘连蛋白 A 的存在下，肌肉纤维内细胞核和肌球蛋白含量明显减少。这导致了一个概念，即剩余的肌核彼此之间非常遥远，并被推向超出其最大细胞质容量的功能，最终导致肌肉纤维无力。
