Sensor kinase regulation in Caulobacter differentiation

描述（由申请人提供）：不对称细胞分裂是细胞分化和新细胞类型产生的基本机制。革兰氏阴性α -变形杆菌新月形Caulobacter crescenus遵循不相等细胞分裂的不变模式，产生两个具有不同结构和发育命运的后代细胞。这种生物现在被认为是研究细胞不对称如何建立及其在发育调节中的作用的理想模型系统。了解这些过程是本应用程序中提出的研究的长期目标。遗传分析表明，这些细胞的发育事件通过由双组分蛋白家族介导的基本信号转导通路网络与细胞周期进程紧密协调。值得注意的是，启动这些途径的传感器激酶，就像它们控制的形态发生事件一样，在空间上定位于细胞极点。本研究的核心工作是了解PleC、DivJ、DivL和CckA激酶亚细胞定位的分子机制，以及定位在激酶功能和调控中的作用。该实验的目的是：(1)对PleC激酶及其同源的必需反应调节因子DivK进行详细的遗传和生化分析，以确定它们在极性形态发生和细胞分裂中的调节作用；(2)鉴定PleC和其他细胞周期调节激酶中指定其亚细胞定位的序列，并研究定位在发育调节中的作用；(3)识别负责这些信号转导蛋白亚细胞定位的细胞机制的元件。

DESCRIPTION (provided by applicant): Asymmetric cell division is a fundamental mechanism for differentiation and the generation of new cell types. The gram negative, alpha-proteobacterium Caulobacter crescentus follows an invarient pattern of unequal cell division to produce two progeny cells with different structures and developmental fates. This organism is now recognized as an ideal model system for the study of how cellular asymmetry is established and its role in developmental regulation. An understanding of these processes is the long-term goal of the research proposed in this application. Genetic analysis has shown that developmental events in these cells are tightly coordinated with cell cycle progression by networks of essential signal transduction pathways mediated by the two-component family of proteins. Remarkably, the sensor kinases that initiate these pathways are, like the morphogenic events they control, spatially localized at the cell poles. A central focus of the proposed work is to understand the molecular mechanisms responsible for the subcellular localization of the PleC, DivJ, DivL and CckA kinases and the role of localization in kinase function and regulation. The aims of the proposed experiments are to: (1) carry out a detailed genetic and biochemical analysis of the PleC kinase and its cognate essential response regulator DivK to define their roles in the regulation of polar morphogenesis and cell division; (2) identify the sequences within PleC and other cell cycle-regulated kinases that specify their subcellular localization and examine the role of localization in developmental regulation; and (3) identify elements of the cellular machinery responsible for subcellular localization of these signal transduction proteins.