Nucleomorphin: a nucleolar calmodulin binding protein that regulates nuclear number

核吗啡：一种调节核数量的核仁钙调蛋白结合蛋白

• 批准号: 6807-2011
• 负责人: ODay, Danton
• 金额: $ 2.62万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=506083
• 关键词: Nucleomorphin; nucleolar; calmodulin; binding; protein

The nucleolus is a special compartment in the cell nucleus that is a central controlling element in cell division of normal and cancer cells. Originally considered simply a ribosome factory it now is known to have many other critical functions. It is involved in the cell cycle, life span, viral replication, molecular sequestering, and stress responses, among other activities. We have discovered and have studied a nucleolar protein called nucleomorphin (NumA1) in Dictyostelium discoideum. Dictyostelium is recognized as a model organism for the study of cell and developmental biology. NumA1 now represents the most well studied nucleolar protein in Dictyostelium. Like nucleolar proteins in humans, NumA1 has nucleolar and nuclear localization signals plus an extensive stretch of acidic amino acids (glutamic acid/aspartic acid). When this acidic amino acid sequence is removed, the cells become highly multinucleated. Cells typically have a single nucleus suggesting NumA1 is involved in the regulation of nuclear number. NumA1 binds to calcium binding protein (CBP4a) in a calcium-dependent manner via this acidic stretch of acids suggesting it too is involved in NumA1 function. We will knockout the gene for CBP4a to learn what its role is in regulating nuclear number and in other cell functions. In other species, nucleolar proteins move back and forth between the nucleolus, nucleoplasm and cytoplasm but exactly how this is controlled remains elusive. We will study the phosphorylation of NumA1 as well as its nucleolar and nuclear localization signals to determine if this is what controls this translocation. Along with related experiments, this work will provide major advances into the roles of two nucleolar proteins in cell function and in how nuclear number is regulated. In the long term, we believe it will set the stage for using Dictyostelium as a model system for the study of nucleolar structure and function in all organisms.

核仁是细胞核中一个特殊的隔室，是正常细胞和癌细胞分裂的中心控制元件。最初认为它只是一个核糖体工厂，现在知道它有许多其他关键功能。它参与细胞周期、寿命、病毒复制、分子隔离和应激反应等活动。我们已经发现并研究了盘状盘齿龙的一种核仁蛋白，称为核胚蛋白（NumA1）。盘基ostelium被认为是研究细胞和发育生物学的模式生物。NumA1现在是盘基骨柱中研究得最多的核仁蛋白。与人类的核仁蛋白一样，NumA1具有核仁和核定位信号以及广泛的酸性氨基酸（谷氨酸/天冬氨酸）。当这个酸性氨基酸序列被移除时，细胞变成高度多核的。细胞通常只有一个细胞核，这表明NumA1参与了细胞核数量的调节。NumA1通过这种酸的酸性延伸以钙依赖的方式与钙结合蛋白（CBP4a）结合，表明它也参与了NumA1的功能。我们将敲除CBP4a基因，以了解其在调节核数和其他细胞功能中的作用。在其他物种中，核仁蛋白在核仁、核质和细胞质之间来回移动，但这究竟是如何控制的仍然难以捉摸。我们将研究NumA1的磷酸化及其核仁和核定位信号，以确定这是否是控制这种易位的原因。随着相关实验的开展，这项工作将为两种核仁蛋白在细胞功能和核数调节中的作用提供重大进展。从长远来看，我们相信这将为利用盘基ostelium作为研究所有生物核仁结构和功能的模型系统奠定基础。