Dynamic remodelling of the muscle-tendon cell contact in Drosophila
果蝇肌肉肌腱细胞接触的动态重塑
基本信息
- 批准号:258684444
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Units
- 财政年份:2014
- 资助国家:德国
- 起止时间:2013-12-31 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Precise coordination of muscle-tendon attachment and myofibrillogenesis is important to form a stable muscle-tendon contact. Without proper coordination premature muscle contractions would destroy an unstable muscle-tendon junction and lead to severe myopathies. By studying the temporal dynamics of muscle-tendon contact formation in Drosophila flight muscle we found that attachment begins as a dynamic cell-cell contact between tendon cells and myotubes, which is mediated by the orphan transmembrane receptor Kon-tiki (Kon). Kon is required in the muscle to mediate cell-cell recognition of the tendons and is concentrated at muscle-tendon contact. This is initial muscle-tendon contact is devoid of ECM, which is only recruited during attachment maturation, to form a stable force-resistant muscle-tendon junction. We found that this remodelling coincides with the formation of mechanical tension within the myotendinous system before simultaneous myofibrillogenesis is triggered in the muscle. In Aim 1 of this proposal we plan to investigate the mechanism how kon mediates attachment initiation. We will investigate the impact of kon removal on the actin and microtubule cytoskeleton. Moreover, we will explore potential links of Kon to Cadherin, which also localises to the muscle-tendon contact. In Aim 2 we will study the contribution of the microtubule cytoskeleton to remodelling of the myotendinous interface and the formation of tension. A combination of functional RNAi data with direct microtubule manipulations should identify important microtubule associated proteins that participate in these processes. In Aim 3 we intend to test the spectraplakin homolog Shortstop (Shot) a role for in attachment and tension formation. Shot is found concentrated at the myotendinous interface and can bind to both microtubules and actin filaments. Thus, Shot may link attachment and the formation of tension to myofibrillogenesis. Together, these experiments should lead to a better understanding of how the remodelling of the muscle-tendon interface from dynamic cell-cell contacts to a stable junction allows formation of tension and can eventually trigger myofibrillogenesis.
肌肉-肌腱附着和肌原纤维发生的精确协调对于形成稳定的肌肉-肌腱接触是重要的。如果没有适当的协调,过早的肌肉收缩会破坏不稳定的肌肉肌腱连接,导致严重的肌病。通过研究果蝇飞行肌中肌-腱接触形成的时间动力学,我们发现附着开始于腱细胞和肌管之间的动态细胞-细胞接触,其由孤儿跨膜受体Kon-tiki(Kon)介导。Kon在肌肉中是介导肌腱的细胞-细胞识别所必需的,并且集中在肌肉-肌腱接触处。这是初始的肌肉-肌腱接触,没有ECM,ECM仅在附着成熟期间被招募,以形成稳定的抗力肌肉-肌腱连接。我们发现,这种重塑与在肌肉中同时触发肌原纤维生成之前在肌腱系统内形成机械张力相一致。在本提案的目标1中,我们计划研究kon如何介导依恋起始的机制。我们将研究去除kon对肌动蛋白和微管细胞骨架的影响。此外,我们将探讨Kon与钙粘蛋白的潜在联系,钙粘蛋白也定位于肌肉-肌腱接触。在目标2中,我们将研究微管细胞骨架对肌腱界面重塑和张力形成的贡献。功能性RNAi数据与直接微管操作的组合应确定参与这些过程的重要微管相关蛋白。在目标3中,我们打算测试spectraplakin同源物Shortstop(Shot)在附着和张力形成中的作用。铅球被发现集中在肌腱界面,可以结合到微管和肌动蛋白丝。因此,Shot可能将附着和张力的形成与肌原纤维发生联系起来。总之,这些实验应该导致更好地了解如何重塑的肌肉肌腱界面从动态细胞-细胞接触到一个稳定的连接允许张力的形成,并最终触发肌原纤维形成。
项目成果
期刊论文数量(0)
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Dr. Frank Schnorrer其他文献
Dr. Frank Schnorrer的其他文献
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