Functional characterization of newly identified inserted membrane proteins of the nuclear envelope

新鉴定的核膜插入膜蛋白的功能表征

• 批准号: 5444355
• 负责人: Dr. Anja Bubeck
• 金额: --
• 依托单位: Department of Cell Biology (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5444355?language=en
• 关键词: Functional; characterization; newly; identified; inserted

The nuclear envelope (NE) constitutes the interface between the nucleus and the cytoplasm. Notwithstanding its role in nuclear structure, increasing evidence indicates that the NE also is involved in regulation of cellular processes. Mutations in genes coding for proteins of the NE can cause a variety of diseases affecting striated muscle. How mutations in these genes, which are ubiquitously expressed lead to a tissue-specific manifestation of disease is not clear. Using comprehensive proteomic methods the Gerace laboratory has recently identified 67 previously uncharacterized integral proteins of the NE. This project will focus on the characterization of the products of a subset of these genes that are located in chromosomal regions linked to mutations causing several types of muscular dystrophies (MDs). We aim to functionally characterize some of these candidate genes with respect to their role in cell organization, function and muscle cell differentiation. To this end, expression of the candidate genes will be individually repressed in a cultured myoblast cell system, to screen for the effects of gene down-regulation on cell growth, nuclear and cytoplasmic organization and on muscle cell differentiation. This study will contribute to the understanding of the function of integral proteins of the NE in cells. The use of a muscle cell model allows further to investigate the function of candidate genes in muscle cell differentiation. This will provide insights into the mechanism by which NE proteins cause MDs and other diseases.

核膜(NE)构成了细胞核和细胞质之间的界面。尽管它在核结构中发挥作用，但越来越多的证据表明，NE也参与了细胞过程的调节。NE蛋白编码基因的突变可导致多种影响横纹肌的疾病。这些普遍表达的基因突变如何导致疾病的组织特异性表现尚不清楚。使用全面的蛋白质组学方法，Gerace实验室最近鉴定了67个以前未描述的NE的完整蛋白质。这个项目将专注于这些基因的一个子集的产物的特征，这些基因位于染色体区域，与导致几种类型的肌肉营养不良(MD)的突变有关。我们的目标是对这些候选基因中的一些在细胞组织、功能和肌肉细胞分化中的作用进行功能表征。为此，候选基因的表达将在培养的成肌细胞系统中被单独抑制，以筛选基因下调对细胞生长、核质组织和肌肉细胞分化的影响。这一研究将有助于了解NE在细胞内的整合蛋白的功能。肌肉细胞模型的使用允许进一步研究候选基因在肌肉细胞分化中的功能。这将为NE蛋白导致MDS和其他疾病的机制提供洞察力。