Myosin-X: A Novel Myosin with PH Domains

Myosin-X：一种具有 PH 结构域的新型肌球蛋白

• 批准号: 6478586
• 负责人: RICHARD E CHENEY
• 金额: $ 30.93万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6478586
• 关键词: actins; biological signal transduction; cell component structure /function; cell components; cell motility; electron microscopy; fluorescence microscopy; genetic regulation; green fluorescent proteins; immunocytochemistry; integrins; intermolecular interaction; intracellular transport; laboratory mouse; laboratory rat; molecular site; myosins; phagocytosis; phosphorylation; protein kinase; protein localization; protein structure function; protein transport; time resolved data; video microscopy; yeast two hybrid system

DESCRIPTION: Myosin-X is an unconventional myosin of the MyTH-FERM super class that is broadly expressed in vertebrate tissues. Although little is known about the functions of the MyTH-FERM myosins, mutations in one member of this group are the leading cause of hereditary deaf-blindness in children. We recently discovered that myosin-X undergoes a novel form of motility within filopodia, and we hypothesize that myosin-X is a component of a widespread but previously uncharacterized system for intracellular transport on actin-rich structures such as filopodia. Myosin-X also exhibits a remarkable localization to the tips of filopodia and overexpressing it leads to increased number and length of filopodia, suggesting that myosin-X functions in the largely unknown pathways regulating filopodial dynamics. Myosin-X also binds to integrins and one of its light chains is known to be dramatically down regulated in many tumors. Together these data strongly suggest that myosin-X and the novel form of motility associated with it play fundamental but largely unexplored roles in the basic cell biology underlying human health and disease. We propose to: I. Determine the fundamental properties, mechanisms, and regulation of this novel form of motility. II. Identify the structures and molecular cargo(s) transported by intrafilopodial motility. III. Use myosin-X as a marker to identify the components of a putative filopodial tip complex and determine if myosin-X is a component of signaling pathways that regulate filopodial dynamics. IV. Determine the functions of myosin-X in key cell biological processes such as phagocytosis, filopodial dynamics, and cell crawling. This research will determine the fundamental properties of a novel and previously uncharacterized form of motility that has critical implications for a host of important cell biological processes including integrin function, cell adhesion, filopodial dynamics, macrophage function, and nerve regrowth. The proposed research will thus answer critical questions about the basic cell biology underlying many human diseases including cancer, hereditary deafness, retinitis pigmentosa, and nerve injury.

描述：肌球蛋白-X是神话超级阶级的非常规的肌球蛋白 这在脊椎动物组织中广泛表达。虽然对 神话肌蛋白的功能，该组一个成员的突变 是儿童世袭聋哑人的主要原因。我们最近 发现肌球蛋白X在丝状虫中经历了一种新型的运动形式， 我们假设肌球蛋白X是广泛的，但以前是 在富含肌动蛋白的结构上细胞内运输的未表征系统 例如丝状。肌球蛋白-X在技巧上也表现出了一个显着的本地化 丝状和过表达的丝虫导致数量和长度增加 丝状肌表明肌球蛋白X在很大程度上未知的途径中起作用 调节丝虫动力学。肌球蛋白X也与整联蛋白及其其中一种结合 已知轻链在许多肿瘤中被大大调节。 这些数据共同表明肌球蛋白X和新颖的形式 与之相关的运动性扮演着基本，但在很大程度上没有探索 人类健康和疾病的基本细胞生物学。我们建议： I.确定此的基本属性，机制和调节 新型运动形式。 ii。确定由运输的结构和分子货物 肾上腺内运动。 iii。使用Myosin-X作为标记来识别假定的组成部分 丝状尖端复合物并确定肌球蛋白-X是否是信号的组成部分 调节丝虫动力学的途径。 iv。确定肌球蛋白X在关键细胞生物学过程中的功能 作为吞噬作用，丝虫动力学和细胞爬行。 这项研究将确定小说和 以前没有特征的运动形式，对 许多重要的细胞生物学过程，包括整合素功能，细胞 粘附，丝状动力学，巨噬细胞功能和神经再生。这 因此，拟议的研究将回答有关基本细胞的关键问题 许多人类疾病的生物学包括癌症，遗传性耳聋， 色素性视网膜炎和神经损伤。