Mutational Studies of Processive Myosin Motors

进行性肌球蛋白运动的突变研究

• 批准号: 7807806
• 负责人: KATHLEEN M TRYBUS
• 金额: $ 19.75万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807806
• 关键词: Actins; COS-7 Cell; Carrier Proteins; Cells; Disease; Human Resources; In Vitro; Kinesin; Life; Mammalian Cell; Microtubules; Molecular Motors; Motor; Movement; Myosin ATPase; Myosin Type V; Occupations; Parents; Property; Proteins; Research; Role; Work; base; human disease; parent grant; public health relevance; research study

DESCRIPTION (provided by applicant): This is a competitive revision of parent grant GM078097, Mutational Studies of Processive Myosin Motors. It seeks to expand the scope of the original application by proposing experiments with motor proteins in cultured mammalian cells, in contrast to the parent application which purely involved in vitro characterization. Moreover, it fulfills both the role of job creation (a new postdoctoral associate will be hired) as well as accelerating the tempo of research by this input of manpower. The first aim seeks to establish what features of myosin V are essential for it to effectively maneuver through the meshwork that constitutes the actin cortex in a living cell. The importance of duty cycle of the motor and motor number per cargo for myosin V based cargo-transport will be determined in COS-7 cells. Secondly, we will investigate how the handoff of cargo, from kinesin-based movement on microtubules to myosin Vbased transport on actin, is facilitated within the cell. Kinesin and myosin V will be attached to the same cargo to follow transport from the cell center out to the periphery. The impact of this work will be to establish the extent to which the basic properties we associate with myosin V and kinesin from in vitro studies are also operative within the cell. A number of human diseases result from disruption of cargo transport along actin or microtubules, or from disease proteins acting as cargo for these transport proteins. A better understanding of the mechanism by which molecular motors move along their track in the cell is critical to further understand the basis of these diseases. PUBLIC HEALTH RELEVANCE: A number of human diseases result from disruption of cargo transport along actin or microtubules, or from disease proteins acting as cargo for these transport proteins. A better understanding of the mechanism by which molecular motors move along their track in the cell is critical to further understand the basis of these diseases.

描述（由申请人提供）：这是对父母赠款GM078097的竞争性修订，即对肌球蛋白电机的突变研究。它试图通过在培养的哺乳动物细胞中使用运动蛋白进行实验来扩大原始应用的范围，与纯粹涉及体外表征的父应用相反。此外，它既履行了创造就业的角色（将被聘用新的博士后助理），还可以通过这种人力的意见来加速研究的节奏。第一个目的旨在确定肌球蛋白V的哪些特征对于它有效地通过构成活细胞中肌动蛋白皮质的网状作品进行操纵至关重要。在COS-7细胞中，将确定每个货物对基于肌球蛋白V的货物传输的电机数量和电动机数量的占空比的重要性。其次，我们将研究货物的交接，从微管上的基于动力蛋白的运动到基于肌动蛋白的肌球蛋白VB的转运，在细胞内促进。动力素和肌球蛋白V将连接到同一货物上，以跟随从细胞中心运输到周围。这项工作的影响是确定我们与体外研究的肌球蛋白V和动力素相关的基本特性在细胞内也有效。许多人类疾病是由于沿肌动蛋白或微管的货物运输的破坏而导致的，或疾病蛋白充当这些转运蛋白的货物。更好地理解分子电动机沿细胞中的轨道移动的机制对于进一步了解这些疾病的基础至关重要。 公共卫生相关性：许多人类疾病是由于沿肌动蛋白或微管的货物中断而导致的许多人类疾病，或者是由作为这些运输蛋白的货物的疾病蛋白引起的。更好地理解分子电动机沿细胞中的轨道移动的机制对于进一步了解这些疾病的基础至关重要。