Sensor kinase regulation in caulobacter differentiation

描述(申请人提供)：不对称细胞分裂是分化和产生新细胞类型的基本机制。革兰氏阴性的α-蛋白杆菌新月弯杆菌遵循不变的细胞分裂模式，产生两个具有不同结构和发育命运的后代细胞。这种生物体现在被认为是研究细胞不对称性如何建立及其在发育调控中的作用的理想模型系统。对这些过程的理解是本申请中提出的研究的长期目标。遗传分析表明，这些细胞中的发育事件与细胞周期进程密切协调，由两组分蛋白质家族介导的重要信号转导网络。值得注意的是，启动这些通路的传感器激酶，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。这项拟议工作的中心焦点是了解Plec、DivJ、DivL和Cck A激酶亚细胞定位的分子机制，以及定位在激酶功能和调节中的作用。这些实验的目的是：(1)对Plec激酶及其同源基本反应调节因子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调控中的作用；(2)确定Plec和其他细胞周期调节蛋白中指定其亚细胞定位的序列，并研究定位在发育调控中的作用；以及(3)确定负责这些信号转导蛋白亚细胞定位的细胞机制元件。

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.