PDF(Pubmed)
Abstract：
Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown in zebrafish or genetic knockout in mice, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one with Styxl2 being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role in de novo sarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions in de novo sarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotes de novo sarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.
摘要：
Styxl2，一种特征不佳的假磷酸酶，在培养的成肌细胞分化过程中被鉴定为Jak1-Stat1途径的转录靶标。Styxl2在脊椎动物横纹肌中特异性表达。通过斑马鱼的基因敲除或小鼠的基因敲除，我们发现Styxl2在维持肌肉发育中的肌节完整性中起着至关重要的作用.为了进一步揭示Styxl2在成人肌肉中的功能，我们产生了两个诱导型敲除小鼠模型：一个在成熟肌纤维中删除Styxl2，以评估其在肌节维持中的作用，另一个在成年肌肉卫星细胞（MuSCs）中评估其在从头肌节组装中的作用。我们发现Styxl2不是肌节维持所必需的，而是在损伤诱导的肌肉再生过程中在从头肌节组装中起作用。机械上,Styxl2与非肌肉肌球蛋白II相互作用，增强了它们的泛素化，并针对它们进行自噬依赖性降解。没有Styxl2，非肌肉肌球蛋白II的降解被延迟，这导致有缺陷的肌节组装和力的产生。因此，Styxl2通过与非肌肉肌球蛋白II相互作用并促进其自噬降解来促进从头肌节组装。
