IN VIVO ASSEMBLY AND DISASSEMBLY PATHWAYS OF CYTOPLASMIC INTERMEDIATE FILAMENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 就像人类的骨骼一样，细胞骨架为单个细胞提供机械支撑。细胞骨架对细胞内的分隔和信号转导通路也是必不可少的。细胞骨架有三种类型：微管、微丝和中间丝。这些细胞骨架系统基本上由简单的亚基组成，这些亚基又形成聚合物，从而形成最终的丝状形式。与分别由胞浆微管蛋白和肌动蛋白形成的微管和微丝不同，中间丝(IF)是由一大家族差异表达的基因形成的。通常，IF可占细胞内总蛋白的1%~5%。IF的紊乱和/或聚集是许多人类疾病的标志。悬而未决的问题是，个体IF亚单位如何在体内组装成细丝，以及细丝如何分解成亚单位。该项目的目标是确定组装和拆卸过程所需的因素，并描绘体内的途径。最后，我们想知道这些途径是否在疾病背景下发生了变化，以及该项目中确定的分子是否可以用作治疗靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Like the skeleton in humans, the cytoskeleton provides the mechanic support for the individual cells. The cytoskeleton is also essential for compartmentation and signal transduction pathways within the cells. There are three types of cytoskeleton: microtubules, microfilaments, and intermediate filaments. These cytoskeletal systems are essentially composed by simple subunits that in turn form polymers to give rise to the final filamentous form. Unlike microtubules and microfilaments, which are formed by cytosolic tubulin and actin, respectively, intermediate filaments (IFs) are formed by a large family of differentially-expressed genes. Typically, IF can take up to 1~5% of total proteins inside the cells. The disorganization and/or aggregation of IF are a hallmark of many human diseases. The outstanding question is how individual IF subunit assemble into filaments and how the filaments disassemble into subunits in vivo. The goal of this project is to identify the factors required for the assembly and disassembly processes and to delineate the in vivo pathways. Finally, we would like to know whether these pathways are altered in the disease settings and whether the molecules identified in this project can be used as therapeutic targets.