Actin Assembly in Non-Motile Cells

肌动蛋白结构对于多细胞生物的许多细胞类型之间的功能和结构差异至关重要。对于不同细胞类型中不同肌动蛋白结构的产生和维持的重要活动还没有很好的理解。 该项目将研究对这些结构的组装重要的蛋白质和活性。 以果蝇为模型系统，在刚毛细胞中研究肌动蛋白组装成丝束的控制。 成体感觉刚毛依赖于肌动蛋白束，在适当的时间和适当的地点组装，以获得其特殊的形状。 加帽蛋白（肌动蛋白组装的调节因子）的功能缺失突变导致肌动蛋白束，从而导致刚毛形状缺陷。当在束组装中与加帽蛋白一起工作的其他肌动蛋白调节剂的量在加帽蛋白突变动物中甚至轻微改变时，观察到肌动蛋白组织的显著变化。 因此，加帽蛋白突变体动物提供了一个敏感的测定系统之间的相互作用肌动蛋白调节。 为了完成这些实验，不同肌动蛋白调节蛋白的数量将通过编码它们的基因突变或增加致敏动物（加帽蛋白突变体）拷贝数的转基因来改变。 将分析固定和活样本中肌动蛋白束的组织和组装。所有真核细胞都依赖肌动蛋白结构生存并执行特定功能。由于肌动蛋白结构及其蛋白质组分在物种间是保守的，因此从这些研究中获得的结果将是普遍适用的。 这项工作也将通过在科学实践中培训本科生、研究生和博士后研究员产生广泛的影响。 此外，这些研究将产生转基因和突变动物的集合，用于对肌动蛋白和不同细胞专业化的发展感兴趣的广泛的细胞生物学家。

Actin structures are critically important for functional and structural differences among the many cell types of multicellular organisms. The activities important for generation and maintenance of the different actin structures in different cell types are not well understood. This project will investigate the proteins and activities important for assembly of some of these structures. Using Drosophila as a model system, control of actin assembly into filament bundles will be studied in bristle cells. The adult sensory bristle relies on actin bundles, assembled at the proper time and proper place, for its specialized shape. Loss of function mutations in capping protein, a regulator of actin assembly, lead to actin bundle and, therefore, bristle shape defects. When amounts of other actin regulators that work with capping protein in bundle assembly are even slightly altered in capping protein mutant animals, striking changes in actin organization are observed. Thus, capping protein mutant animals provide a sensitive assay system for interactions among actin regulators. To accomplish these experiments, the amounts of different actin regulatory proteins will be altered using mutations in the genes that encode them or transgenes that increase copy number in sensitized [capping protein mutant] animals. The organization and assembly of actin bundles in fixed and live samples will be analyzed. All eukaryotic cells rely on actin structures to live and perform specialized functions. Because actin structures and their protein constituents are conserved across species, the results obtained from these studies will be generally applicable. This work will also have broad impact through training of undergraduates, graduate students, and post-doctoral fellows in the practice of science. In addition, these studies will generate collections of transgenic and mutant animals that are of use to a broad array of cell biologists interested in actin and in the development of different cellular specializations.