Myosin-X and the molecular basis of filopodia function

肌球蛋白-X 和丝状伪足功能的分子基础

基本信息

批准号：
8701268
负责人：
RICHARD E CHENEY
金额：
$ 31.95万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-06-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8701268
关键词：
Actins Adhesions Adhesives Affinity Area Binding Biological Models Biological Process Biosensor Cell Adhesion Cell Surface Receptors Cells Cellular Structures Cellular biology Complex Cytoskeleton Defect Disease Environment Equilibrium Filopodia Fingers Fluorescence Recovery After Photobleaching Focal Adhesions Goals Growth Head Health Hearing Human Image Imaging Device Integrins Investigation Knowledge Life Ligands Link Mechanics Membrane Microfilaments Molecular Movement Myosin ATPase Nature Neoplasm Metastasis Nerve Process Property Proteins Public Health Research Role Signal Pathway Signal Transduction Signaling Protein Site Stereocilium Structure System Tail Work Wound Healing angiogenesis base cellular imaging cellular microvillus deafness human disease innovation neurodevelopment novel optical traps photoactivation polymerization public health relevance sensor single molecule synaptogenesis tool transmission process

项目摘要

DESCRIPTION (provided by applicant): Filopodia are finger-like cellular protrusions hypothesized to act as sensors that allow cells to contact and interact with their environment. Filopodia are known or hypothesized to have key roles in processes such as nerve growth, angiogenesis, wound healing, and hearing. Structurally related protrusions known as stereocilia function as mechanosensors responsible for our senses of hearing and balance, and defects in the assembly of stereocilia, or in the unconventional myosins that localize to them, cause many forms of human deafness. Although the tips of filopodia, microvilli, and stereocilia all contain a specialized structure known as the tip complex, remarkably little is known about the basic properties of the tip complex, even though it clearly represents a key site of cell contact and interaction that is also important in the formation of these protrusions. Our discovery that myosin-X (Myo10) localizes to the tips of filopodia and binds to ¿-integrins has led us to hypothesize that Myo10 is a central component of the filopodial tip complex, and that the tip complex is a specialized site of polymerization, adhesion, and signaling. Since very little is known about the filopodial tip complex, especially in comparison to intensively studied adhesive structures such as focal adhesions, our objective is to determine the basic properties of the filopodial tip complex and define its roles in filopodial adhesion and signaling. Our specific aims are to: 1) Determine the composition and properties of the filopodial tip complex. 2) Visualize the formation and dynamics of the tip complex and investigate its role in cell signaling. 3) Determine the functions of the filopodial tip complex in adhesion and mechanotransduction. By defining the basic properties of the filopodial tip complex, this research will provide fundamental information needed to understand key cell biological processes underlying human health and disease. In addition, studies of Myo10 and the filopodial tip complex provide a model system for understanding the functions of unconventional myosins in stereocilia and other structures based on actin bundles.

描述（适用提供）：丝状虫是指的类似手指的细胞蛋白，据称是允许细胞接触并与环境相互作用的传感器。已知或假设的丝状症在神经生长，血管生成，伤口愈合和听力等过程中具有关键作用。结构相关的蛋白质被称为立体胶质的蛋白质充当负责我们的听力和平衡感的机制，尽管在丝状，微绒毛和立体胶体的尖端中的缺陷以及缺陷都包含一种特殊的尖端结构，但它们都包含了尖端复合物的特殊结构，即使是尖端复合物的基本特性，但它显然代表了键位的基本特性，也代表了一个键位的键入和互动的键入。我们发现，肌球蛋白-X（MyO10）定位于丝状尖端并与� -integin结合的尖端使我们假设Myo10是丝状尖端复合物的中心成分，并且尖端配合物是聚合，粘合剂，粘合剂和信号传导的专业位点。由于对丝状尖端复合物知之甚少，尤其是与经过深入研究的粘合剂结构（例如焦点粘合剂）相比，我们的目标是确定丝状尖端复合物的基本特性，并定义其在丝状粘合剂和信号传导中的作用。我们的具体目标为：1）确定丝状尖端复合物的组成和特性。 2）可视化尖端复合物的形成和动力学，并研究其在细胞信号传导中的作用。 3）确定在粘合剂和机械传导中丝端尖端复合物的功能。通过定义丝状尖端复合体的基本特性，这项研究将提供基本了解人类健康和疾病基础的关键细胞生物过程所需的信息。此外，对Myo10和丝状尖端复合物的研究提供了一个模型系统，用于了解基于肌动蛋白束的立体胶质和其他结构中非常规肌球蛋白的功能。