Myosin-X: A Novel Myosin with PH Domains

描述：肌球蛋白-X是一种非常规肌球蛋白，属于神话-蕨类超级体。 在脊椎动物组织中广泛表达。尽管人们对此知之甚少 神话-变种肌球蛋白的功能，这一组中的一个成员的突变 是导致儿童遗传性失聪的主要原因。我们最近 发现肌球蛋白-X在丝状伪足中经历了一种新的运动形式， 我们假设肌球蛋白-X是一种广泛的但之前 富含肌动蛋白的结构上细胞内转运的未知系统 例如丝状伪足。肌球蛋白-X也表现出对尖端的显著定位 丝状伪足的数量和长度的增加和过度表达会导致 丝状伪足，提示肌球蛋白-X在很大程度上未知的途径中发挥作用 调节丝状轴的动态。肌球蛋白-X还与整合素和其一个 已知轻链在许多肿瘤中显著下调。 综上所述，这些数据强烈表明，肌球蛋白-X和新形式的 与之相关的运动性在其中扮演着基本但在很大程度上未被探索的角色 人类健康和疾病的基础细胞生物学。我们建议： 一、确定其基本属性、机制和调控 新的运动形式。 二、鉴定运输的结构和分子货物(S) 细丝内径运动。 使用肌球蛋白-X作为标记物来鉴定推定的 丝状末端复合体和确定肌球蛋白-X是否是信号成分 调节丝状细胞动力学的途径。 确定肌球蛋白-X在关键细胞生物学过程中的功能 如吞噬、丝状尿路动力学和细胞爬行。 这项研究将决定一部小说和一部 一种以前没有特征的运动形式，它对 一系列重要的细胞生物学过程，包括整合素功能，细胞 黏附、丝径动力学、巨噬细胞功能和神经再生。这个 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基础，包括癌症，遗传性耳聋， 视网膜色素变性和神经损伤。

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.