INTERMEDIATE FILAMENT CELL SURFACE INTERACTIONS

这些研究的目的是确定哺乳动物细胞中中间丝及其相关蛋白的结构和功能。 中间丝是主要的细胞骨架结构，其组成蛋白质以细胞类型特异性方式变化。 拟议的研究的具体目标是确定中间丝网络组装的机制，中间丝与微管的相互作用，以及它们的动态和运动特性的调节。 在这些研究中采用的技术包括光学和电子显微镜，单细胞显微注射方法，蛋白质的生物化学表征，以及在培养的哺乳动物细胞中克隆和转染野生型和突变型cDNA。 这些研究的结果与人类健康有关，因为已经证明，存在与包含中间丝的结构蛋白的突变相关的许多疾病，并且存在其中中间丝的异常积累是疾病的病理标志的其他疾病。 后者包括酒精性肝病中的马洛里小体和帕金森病中的路易小体的形成。

The goals of these studies are to determine the structure and function of intermediate filaments and their associated proteins in mammalian cells. Intermediate filaments are major cytoskeletal structures and their constituent proteins vary in a cell type specific fashion. The specific aims of the proposed research are to determine the mechanisms underlying the assembly of intermediate filament networks, the interactions of intermediate filaments with microtubules, and the regulation of their dynamic and motile properties. The techniques employed in these studies include light and electron microscopy, single cell microinjection methods, biochemical characterization of proteins, and the cloning and transfection of wild type and mutant cDNAs in cultured mammalian cells. The results of these studies are related to human health as it has been demonstrated that there are many diseases linked to mutations in the structural proteins comprising intermediate filaments and there are other diseases in which abnormal accumulations of intermediate filaments are a pathological hallmark of disease. The latter include the formation of Mallory bodies in alcoholic liver disease and Lewy bodies in Parkinson's disease.