Actin-microtubule interaction-Myosin VI and D-CLIP-190

描述(由申请人提供)： 细胞和发育生物学中的一个重要问题是了解肌动蛋白和微管细胞骨架之间的协调是如何实现的。这项建议旨在通过探索肌动蛋白马达肌球蛋白VI和微管结合蛋白D-CLIP-190之间的相互作用来解决这一问题。将进行生化分析，以确定这两种蛋白质之间的关联是如何调节的。此外，这些蛋白质的相互作用结构域将被绘制出来。最后，使用在本工作过程中开发的试剂，将探索这种相互作用在体内的功能相关性。这项工作将以果蝇黑腹果蝇为模型系统。该系统既适用于生化实验，又能解决体内许多不同细胞和组织类型中感兴趣的分子的功能。由于蛋白质在不同物种之间的分子和功能保守，这项工作应该扩大我们对所有生物中肌动蛋白和微管细胞骨架之间相互作用的理解。这两个细胞骨架系统对细胞功能的几乎所有方面都是至关重要的，包括那些在癌症状态下出现问题的功能。因此，更多地了解它们如何在正常细胞中以协调方式发挥作用，将有助于我们了解癌症的原因和机制。

DESCRIPTION (provided by applicant): An important problem in cell and developmental biology is to understand how coordination between the actin and microtubule cytoskeletons is achieved. This proposal aims to address this by exploring the interaction between an actin motor, myosin VI, and a microtubule binding protein, D-CLIP-190. Biochemical assays will be performed to determine how the association between these two proteins is regulated. Furthermore, the interacting domains of these proteins will be mapped. Finally, using reagents developed in the course of this work, the in vivo functional relevance of this interaction will be explored. This work will utilize the fruit fly Drosophila melanogaster as a model system. This system is ideally suited both for biochemical experiments as well as enabling one to address the functions of molecules of interest in many different cell and tissue types in vivo. Because of the molecular and functional conservation of proteins across species, this work should expand our understanding of the interaction between the actin and microtubule cytoskeletons in all organisms. These two cytoskeletal systems are vital to nearly all aspects of cellular function, including those functions that go awry in cancerous states. Thus, learning more about how they function in a coordinated way in normal cells will aid us in understanding the causes and mechanisms of cancer.