Bacterial Mechanisms for Establishing and Maintaining Cell Polarity

项目摘要 许多棒状细菌都是两极分化的，这意味着细胞的一端是两极分化的。 在形态和功能上与另一个不同，但普遍缺乏 了解极性不对称建立的机制， 树立政治意识由于偏振特征为许多过程提供了关键的空间线索， 包括染色体分离和细胞生长，了解其分子基础 “细菌解剖学”将为原核细胞提供根本性的进步 physiology.此外，一些病原菌利用细胞极性来产生多重 在支持毒力方面具有特殊作用的细胞类型。了解细胞极性 因此，这一背景可能提供与核心机制有关的基本发现 细菌的致病性。 是什么使两极处于不平衡状态？这个项目的重点是分子 控制极性蛋白质和极性组织之间相互作用的机制 一种叫做PopZ的蛋白质，它在柄杆菌的两个细胞极形成聚合物支架 crescentus。该方法从PopZ是一种分子的令人惊讶的发现延伸到 通过与大量绑定直接交互来组织计算单元的集线器 伙伴这意味着有一个选择机制，支持两个并行的 程序的PopZ依赖性多蛋白复合物组装在相反的两端， cell. 该提案包括一系列的实验，将阐明选择 机制使用一组已建立的PopZ结合配偶体，结构和 生物物理分析将用于理解在特定条件下的结合和结合动力学。 原子尺度一个特别关注的领域将是一个内在的无序区域， 决定结合特异性的PopZ。这些实验将提供关键的 开发集线器网络组装的详细生物物理模型的信息， 功能第二个目标是测试不同的模型，以建立和维护 柄杆菌属的极性一种可能性是使用稳定的结合伴侣来标记 一个是“老”极，另一个是每个极都有一套不同的信号蛋白， 通过信号反馈回路加强极性。

PROJECT SUMMARY Many rod-shaped bacteria are polarized, meaning that one end of the cell is morphologically and functionally distinct from the other, but there is a general lack of understanding of the mechanisms by which polar asymmetry is established and maintained. Since polarized features provide critical spatial cues for many processes, including chromosome segregation and cell growth, learning the molecular basis for this `bacterial anatomy' will provide fundamental advancements in prokaryotic cell physiology. Furthermore, some pathogenic bacteria use cell polarity to create multiple cell types with specialized roles in supporting virulence. Understanding cell polarity in this context may therefore provide fundamental discoveries relating to core mechanisms for bacterial pathogenicity. What keeps the poles in a state of disequilibrium? This project focuses on the molecular mechanisms that control the interactions between polar proteins and a polar organizing protein, called PopZ, which forms polymeric scaffolds at both cell poles in Caulobacter crescentus. The approach extends from the surprising discovery that PopZ is a molecular hub that organizes the cell by directly interacting with a large number of binding partners. This implies that there is a selection mechanism that supports two parallel programs for PopZ-dependent multiprotein complex assembly at opposite ends of the cell. The proposal includes a series of experiments that will elucidate the selection mechanism. Using a group of established PopZ binding partners, structural and biophysical analyses will be used to understand binding and binding kinetics at the atomic scale. An area of particular focus will be an intrinsically disordered region within PopZ that determines binding specificity. These experiments will provide critical information in developing a detailed biophysical model of hub network assembly and function. The second aim is to test different models for establishing and maintaining polarity in Caulobacter. One possibility is that stable binding partners are used to mark an `old' pole, another is that each pole has a different set of signaling proteins that reinforce polarity through signal feedback loops.