Role and dynamic behavior of cyclic di-GMP signaling proteins in development and cell cycle control

新月柄杆菌细胞极性和细胞周期进程的振荡全球转录调控和空间动态磷酸信号和蛋白水解途径。最近的研究已经确定了第二信使c-di-GMP作为这个调控网络的一个组成部分。然而，这些监管过程中涉及的许多组成部分仍有待确定或尚未进行详细研究。在这里，我们建议分析一个多组分的蛋白质降解平台，它组装在c-di-GMP效应蛋白PopA周围，负责G1-S相变期间几个关键蛋白质的降解。在c-di-GMP结合后，PopA定位于旧细胞极，在那里它募集辅助因子和底物蛋白以递送至极性ClpXP蛋白酶。我们建议定义整个PopA控制模块，包括上游二鸟苷酸环化酶（c-di-GMP合成）和磷酸二酯酶（c-di-GMP降解），以表征用于PopA激活和亚细胞定位的机制，并定义PopA的特定靶蛋白及其在细胞周期依赖性降解中的作用。这些研究将在分子和细胞水平上提供对c-di-GMP介导的蛋白质降解机制的深入了解，并将有助于对C.新月形模式生物

Caulobacter crescentus cell polarity and cell cycle progression are implemented by oscillating global transcriptional regulators and by spatially dynamic phospho-signaling and proteolysis pathways. Recent studies have identified the second messenger c-di-GMP as an integral part of this regulatory network. However, many of the components involved in these regulatory processes are still waiting to be identified or have not been studied in detail. Here we propose to analyze a multicomponent protein degradation platform, which assembles around the c-di-GMP effector protein PopA and is responsible for the degradation of several key proteins during G1-S phase transition. Upon binding of c-di-GMP, PopA localizes to the old cell pole, where it recruits accessory factors and substrate proteins for delivery to the polar ClpXP protease. We propose to define the entire PopA control module, including upstream diguanylate cyclases (c-di-GMP synthesis) and phosphodiesterases (c-di-GMP degradation), to characterize the mechanism used for PopA activation and subcellular localization, and to define the specific target proteins of PopA and their role in cell cycle dependent degradation. These studies will provide an in-depth view on c-di-GMP mediated protein degradation mechanisms at the molecular and cellular level and will help to generate a global and quantitative understanding of the c-di-GMP signaling network in the C. crescentus model organism.