PROTEINS INTERACTING WITH THICK FILAMENT ASSEMBLY

描述：该提案涉及重要的一般生物学 精确组织的受管制的集会的机制问题 细胞内结构，更具体地说， 在骨骼肌的肌节内形成细丝。 的目标 建议是测试的假设，自我组装的收缩 蛋白质由另外的肌节蛋白引导。 这是一个假设 这是一个长期的调查结果， C.中粗丝组装研究优雅 采取方法是 利用研究人员最近发现的其他相关蛋白质， 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 一组是粗丝的结构成分。 这些 另外的蛋白质被称为肌球蛋白组装酶 催化和杆偶联蛋白，其化学计量地在 引导组件为细丝提供刚性。 前者是 Unc-45基因的产物，后者是蛋白质家族 命名为细丝蛋白a、B和g。利用各种基因，分子 PI将使用遗传学、免疫学、生物化学和成像方法 他的模型系统来证明他的假设的正确性 并将观察扩展到果蝇和小鼠，以证明它们之间的共同点。 跨门的机械主题。

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.