Understanding PP2A phosphatase function in the early C. elegans embryo

了解早期秀丽隐杆线虫胚胎中 PP2A 磷酸酶的功能

• 批准号: 341474-2013
• 负责人: Srayko, Martin
• 金额: $ 2.62万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=549363
• 关键词: Understanding; PP2A; phosphatase; function; early

When cells divide, a multitude of processes must occur at the correct time and in the correct manner. One way that cells orchestrate events required for cell division is by turning on or off the individual components used to accomplish different tasks. Such switches in protein activity can be accomplished by modifying the proteins after they are made. One of the most common ways to modify protein function is through the addition or removal of a phosphate group to the protein. Specific enzymes are used for this: kinases add phosphate groups and phosphatases remove them. These two classes of enzymes are extremely important for the regulation of all cellular processes. There are hundreds of different kinases and phosphatases, and each one can perform very specific roles. We study a phosphatase that is implicated in regulating the assembly and function of a structure that forms only when cells divide. This structure, the mitotic spindle, is used to physically pull chromosomes apart and place them into the future daughter cells as the cell divides. The mitotic spindle consists of, among other components, long rigid fibres called microtubules. The phosphatase we study controls the formation of these fibres and it is essential for proper mitotic spindle assembly. To understand how this phosphatase functions, we will use a combined genetics and biochemical approach to identify any proteins that might regulate its activity, as well as any proteins that the phosphatase directly controls. This phosphatase is also involved in other cellular processes, and we and interested in determining how it can perform multiple tasks at the same time, in the same cell. In order to study the behaviour of the phosphatase in living cells, we are developing innovative microscopy approaches to track the dynamic movement of the phosphatase enzyme as it performs its normal functions. This work will help us understand how cells regulate microtubule fibres to build complex three-dimensional structures such as the mitotic spindle.

当细胞分裂时，许多过程必须在正确的时间以正确的方式发生。 细胞协调细胞分裂所需事件的一种方式是打开或关闭用于完成不同任务的各个组件。 这种蛋白质活性的转换可以通过在蛋白质产生后对其进行修饰来实现。 修饰蛋白质功能的最常见方法之一是通过向蛋白质添加或去除磷酸基团。 特定的酶用于此：激酶添加磷酸基团，磷酸酶去除它们。 这两类酶对所有细胞过程的调节都非常重要。有数百种不同的激酶和磷酸酶，每一种都可以发挥非常特定的作用。 我们研究了一种磷酸酶，它参与调节只有在细胞分裂时才形成的结构的组装和功能。 这种结构，即有丝分裂纺锤体，在细胞分裂时用于物理地将染色体分开并将它们放入未来的子细胞中。 有丝分裂纺锤体由称为微管的长而硬的纤维组成。 我们研究的磷酸酶控制着这些纤维的形成，它对正确的有丝分裂纺锤体组装至关重要。 为了了解这种磷酸酶的功能，我们将使用遗传学和生物化学相结合的方法来鉴定可能调节其活性的任何蛋白质，以及磷酸酶直接控制的任何蛋白质。 这种磷酸酶也参与其他细胞过程，我们有兴趣确定它如何在同一细胞中同时执行多项任务。为了研究磷酸酶在活细胞中的行为，我们正在开发创新的显微镜方法来跟踪磷酸酶在执行其正常功能时的动态运动。 这项工作将帮助我们了解细胞如何调节微管纤维以构建复杂的三维结构，如有丝分裂纺锤体。