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是一种非传统的MyTH-FERM超类肌球蛋白 在脊椎动物组织中广泛表达。尽管我们对 MyTH-FERM肌球蛋白的功能，该组中一个成员的突变 是导致儿童遗传性眼盲的主要原因。我们最近 发现肌球蛋白X在丝状伪足内经历了一种新的运动形式， 我们假设肌球蛋白X是一种广泛存在的，但以前 在富含肌动蛋白的结构上进行细胞内转运的未表征的系统 例如丝状伪足。肌球蛋白-X也表现出显着的本地化的提示 并过度表达它会导致丝状伪足的数量和长度增加， 丝状伪足，这表明肌球蛋白X在很大程度上未知的途径中发挥作用 调节丝状伪足动力学。肌球蛋白X还与整联蛋白及其一种结合 已知轻链在许多肿瘤中显著下调。 总之，这些数据有力地表明，肌球蛋白X和新形式的 与之相关的运动性在 人类健康和疾病的基础细胞生物学。我们建议： I.确定的基本属性，机制，和调节这一点 一种新的运动形式 二.识别通过运输的结构和分子货物 丝状伪足内运动 三.使用肌球蛋白-X作为标记物来鉴定一种假定的 丝状伪足尖端复合体，并确定肌球蛋白-X是否是信号传导的组分 调节丝状伪足动力学的途径。 四.确定肌球蛋白-X在关键细胞生物学过程中的功能， 如吞噬作用、丝状伪足动力学和细胞爬行。 这项研究将确定一部小说的基本性质， 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、丝状伪足动力学、巨噬细胞功能和神经再生。的 因此，拟议中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基础，包括癌症，遗传性耳聋， 视网膜色素变性和神经损伤。