Leiomodin 3 and tropomodulin 4 have overlapping functions during skeletal myofibrillogenesis
Leiomodin 3 and tropomodulin 4 have overlapping functions during skeletal myofibrillogenesis
复制标题
DOI：
10.1242/jcs.152702
复制
发表时间：
2015-01-15
影响因子：
4
通讯作者：
Krieg, Paul A.
中科院分区：
文献类型：
--
作者：
Nworu, Chinedu U.;Kraft, Robert;Krieg, Paul A.
细丝长度的精确调节是必不可少的最佳力量产生在肌肉收缩。细丝旋盖蛋白原调剂蛋白（troomodulin, Tmod）通过调节细丝末端的伸长率和解聚来维持细丝长度的均匀性。leomodins （Lmod1-3）在结构上与Tmod1-4相关，也定位于肌动蛋白丝尖端，但体外生化研究表明Lmods作为强大的成核器。在这里，我们研究了Tmod4和Lmod3在爪蟾骨骼肌纤维病变发生中的作用。Tmod4或Lmod3的缺失导致肌节组装的严重破坏和胚胎运动受损。值得注意的是，当Tmod4缺陷胚胎补充额外的Lmod3和Lmod3缺陷胚胎补充额外的Tmod4时，肌节组装得以恢复，胚胎运动得到改善。这些结果首次表明，适当水平的Tmod4和Lmod3都是胚胎肌纤维形成所必需的，出乎意料的是，这两种蛋白在体内骨骼肌细丝组装过程中都能发挥冗余作用。此外，这些研究证明了非洲爪蟾在分析肌原纤维组装过程中收缩蛋白功能的价值。
Precise regulation of thin filament length is essential for optimal force generation during muscle contraction. The thin filament capping protein tropomodulin (Tmod) contributes to thin filament length uniformity by regulating elongation and depolymerization at thin filament ends. The leiomodins (Lmod1-3) are structurally related to Tmod1-4 and also localize to actin filament pointed ends, but in vitro biochemical studies indicate that Lmods act instead as robust nucleators. Here, we examined the roles of Tmod4 and Lmod3 during Xenopus skeletal myofibrillogenesis. Loss of Tmod4 or Lmod3 resulted in severe disruption of sarcomere assembly and impaired embryonic movement. Remarkably, when Tmod4-deficient embryos were supplemented with additional Lmod3, and Lmod3-deficient embryos were supplemented with additional Tmod4, sarcomere assembly was rescued and embryonic locomotion improved. These results demonstrate for the first time that appropriate levels of both Tmod4 and Lmod3 are required for embryonic myofibrillogenesis and, unexpectedly, both proteins can function redundantly during in vivo skeletal muscle thin filament assembly. Furthermore, these studies demonstrate the value of Xenopus for the analysis of contractile protein function during de novo myofibril assembly.