Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, Hungary.
Elife. 2022 Aug 5;11:e75863. doi: 10.7554/eLife.75863.
Today septins are considered as the fourth component of the cytoskeleton, with the Septin7 isoform playing a critical role in the formation of higher-order structures. While its importance has already been confirmed in several intracellular processes of different organs, very little is known about its role in skeletal muscle. Here, using Septin7 conditional knockdown (KD) mouse model, the C2C12 cell line, and enzymatically isolated adult muscle fibers, the organization and localization of septin filaments are revealed, and an ontogenesis-dependent expression of Septin7 is demonstrated. KD mice displayed a characteristic hunchback phenotype with skeletal deformities, reduction in in vivo and in vitro force generation, and disorganized mitochondrial networks. Furthermore, knockout of Septin7 in C2C12 cells resulted in complete loss of cell division while KD cells provided evidence that Septin7 is essential for proper myotube differentiation. These and the transient increase in Septin7 expression following muscle injury suggest that it may be involved in muscle regeneration and development.
今天，septins 被认为是细胞骨架的第四种成分，其中 Septin7 同工型在形成更高阶结构中起着关键作用。虽然它在不同器官的几个细胞内过程中的重要性已经得到证实，但关于它在骨骼肌中的作用却知之甚少。在这里，我们使用 Septin7 条件性敲低 (KD) 小鼠模型、C2C12 细胞系和酶分离的成年肌肉纤维，揭示了 septin 纤维的组织和定位，并证明了 Septin7 的发育依赖性表达。KD 小鼠表现出特征性的驼背表型，伴有骨骼畸形、体内和体外肌力生成减少以及线粒体网络紊乱。此外，Septin7 在 C2C12 细胞中的敲除导致细胞分裂完全丧失，而 KD 细胞提供的证据表明 Septin7 对于适当的肌管分化是必不可少的。这些以及肌肉损伤后 Septin7 表达的短暂增加表明它可能参与肌肉再生和发育。
