IN VIVO ASSEMBLY AND DISASSEMBLY PATHWAYS OF CYTOPLASMIC INTERMEDIATE FILAMENTS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 像人类的骨骼一样，细胞骨架为单个细胞提供机械支持。细胞骨架对于细胞内的区室化和信号转导途径也是必不可少的。有三种类型的细胞骨架：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以产生最终的丝状形式。不同于微管和微丝，这是由细胞质微管蛋白和肌动蛋白，分别形成，中间丝（IF）是由一个大家庭的差异表达的基因。通常，IF可以占据细胞内总蛋白质的1~5%。IF的解体和/或聚集是许多人类疾病的标志。突出的问题是单个IF亚基如何组装成细丝以及细丝如何在体内分解成亚基。本项目的目标是确定组装和拆卸过程所需的因素，并描绘体内途径。最后，我们想知道这些途径是否在疾病环境中发生改变，以及该项目中鉴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.