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Regulation of myosin VI motor activity by cargo binding in vivo and in vitro

通过体内和体外货物结合调节肌球蛋白 VI 运动活性

基本信息

批准号：
BB/K001981/1
负责人：
Folma Buss
金额：
$ 61.21万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FK001981%2F1
关键词：
Regulation myosin VI motor activity

项目摘要

The biological cell resembles a very busy miniature factory with a large collection of dedicated protein machines working together to maintain the health and welfare of the cell. These machines have highly specific functions and are driven by chemical energy to perform a variety of different tasks. One example are the highly specialized motor proteins that can move along filament tracks in a step-by-step motion powered by the chemical energy derived from ATP hydrolysis. These motor proteins move cargo around the cell to specific locations rather like a train running along a railway network to its specific destination. There are 3 types of motors that work on either large microtubule bundles or actin filament networks, which spread like spider's webs all over the cell. Our research focuses on the molecular motor protein myosin 6, which is unique, because it is the only myosin motor that comes with a reverse gear and therefore can move in the opposite direction to all the other molecular motors along actin filaments. The cargo is hooked up to this motor with the help of a large number of specific adaptor proteins that we have recently identified. The aim of our research is to determine how the specific cargo molecules are selected and attached to the motor and how this triggers the motor to start to move to its destinations in the cell. In addition it is important to understand how this molecular machine is controlled and regulated by identifying its on/off switches, since defects in myosin 6 can cause a number of diseases including deafness and also potentially Alzheimer's disease and prostate cancer. We thus intend to identify the mechanisms that regulate myosin 6 and its adaptor proteins for the transport of cargo to specific regions of the cell. This work will open up new areas of research that will guide future clinical studies and the development of potential diagnostic tools and possible therapeutic strategies to treat dementia and cancer.

生物细胞就像一个非常繁忙的忙碌微型工厂，有大量专门的蛋白质机器一起工作，以维持细胞的健康和福利。这些机器具有高度特定的功能，并由化学能驱动以执行各种不同的任务。一个例子是高度特化的马达蛋白，它可以在ATP水解产生的化学能的驱动下，沿着沿着细丝轨迹一步一步地移动。这些马达蛋白将细胞内的货物运送到特定的位置，就像火车沿着沿着的铁路网驶向特定的目的地一样。有3种类型的马达作用于大的微管束或肌动蛋白丝网络，它们像蜘蛛网一样遍布细胞。我们的研究集中在分子马达蛋白肌球蛋白6，这是独一无二的，因为它是唯一的肌球蛋白马达，带有反向齿轮，因此可以沿着沿着肌动蛋白丝以与所有其他分子马达相反的方向运动。在我们最近发现的大量特异性衔接蛋白的帮助下，货物被连接到这个马达上。我们研究的目的是确定特定的货物分子是如何被选择并附着在马达上的，以及这是如何触发马达开始移动到细胞中的目的地的。此外，重要的是要了解这种分子机器是如何通过识别其开/关开关来控制和调节的，因为肌球蛋白6的缺陷会导致许多疾病，包括耳聋，也可能导致阿尔茨海默病和前列腺癌。因此，我们打算确定的机制，调节肌球蛋白6和它的衔接蛋白的货物运输到细胞的特定区域。这项工作将开辟新的研究领域，指导未来的临床研究，开发潜在的诊断工具和治疗痴呆症和癌症的可能治疗策略。