PROTEINS INTERACTING WITH THICK FILAMENT ASSEMBLY

描述：这项提案涉及重要的普通生物学 精准组织的规整集结机制问题 细胞内结构，更具体地说是如何厚的问题 细丝形成于骨骼肌的肌节内。的目标是 建议检验这样一种假设，即收缩的自组装 蛋白质是由额外的肌节蛋白引导的。这只是一种假设 从长期的调查中得出的建议，由 研究人员对线虫中的粗丝组装进行了调查。方法是 利用研究人员对相关额外蛋白质的最新发现 与主要的粗丝蛋白，肌球蛋白A，B，C，D和 副肌球蛋白。他假设这些相关蛋白质促进了组装 这一组是粗丝的结构成分。这些 其他蛋白质被指定为肌球蛋白组装酶，它起作用 催化和杆状偶联蛋白的化学计量作用 为细丝提供刚性的导向组件。前者是 UNC-45基因的产物和后者是一个蛋白质家族 指定的细丝蛋白，a，b和g。使用各种遗传，分子 PI将使用遗传、免疫学、生化和成像方法 证明其假说正确性的线虫模型系统 并将观察扩展到果蝇和老鼠身上，以展示共同的 整个门的机械论主题。

DESCRIPTION: This proposal addresses the important general biological problem of the mechanisms of regulated assembly of precisely organized intracellular structures and more specifically the problem of how the thick filaments form within sarcomeres of skeletal muscle. The goal of the proposal is to test the hypothesis that self-assembly of contractile proteins is guided by additional sarcomere proteins. This is a hypothesis driven proposal that emerges from a long term set of investigations by this investigator into thick filament assembly in C. elegans. The approach is to exploit the investigator's recent findings of additional proteins associated with the principal thick filament proteins, myosin A, B, C, D and paramyosin. He postulates that these associate proteins facilitate assembly and that one group is a structural component of thick filaments. These additional proteins are designated as myosin assemblase which act catalytically and rod coupling proteins which act stoichiometrically in directing assembly providing rigidity to the filaments. The former is the product of the Unc-45 gene and the latter are a family of proteins designated filagenins, a, b and g. Using a variety of genetic, molecular genetic, immunological, biochemical, and imaging approaches the PI will use the nematod model system to demonstrate the correctness of his hypothesis and extend the observations into Drosophila and mice to demonstrate common mechanistic themes across phyla.