A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression
A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression
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DOI：
10.1073/pnas.0604554103
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发表时间：
2006-07-18
影响因子：
11.1
通讯作者：
Shapiro, Lucy
中科院分区：
文献类型：
--
作者：
Iniesta, Antonio A.;McGrath, Patrick T.;Shapiro, Lucy
时间和空间控制的主调节因子通过调节> 200个基因的表达来驱动柄杆菌属细胞周期。通过ClpXP蛋白酶快速清除主调节因子CtrA是一个关键事件，其使得能够在细胞周期中的特定时间启动染色体复制。我们在这里表明，一个以前未识别的单域响应调节，CpdR，当在非磷酸化状态下，结合到CIpXP，从而导致其本地化的细胞极。我们进一步表明，CIpXP定位所需的CtrA蛋白水解。当CpdR被磷酸化时，ClpXP被离域，并且CtrA不被降解。CtrA和CpdR都通过相同的CckA组氨酸激酶磷酸信号传导途径磷酸化，提供了一种增强机制，该机制同时激活CtrA并通过使CpdR/ClpXP复合物离域来防止其降解。在蜂群细胞中，CpdR处于磷酸化状态，从而防止ClpXP定位和CtrA降解。随着群集细胞分化成柄细胞（Gi/S转换），未磷酸化的CpdR积累并定位于柄细胞极，在那里它使ClpXP定位和CtrA蛋白水解成为可能，从而允许DNA复制的起始。磷酸化信号通路介导的蛋白酶动态定位是一种整合时空调控细菌细胞周期进程的新机制。
Temporally and spatially controlled master regulators drive the Caulobacter cell cycle by regulating the expression of > 200 genes. Rapid clearance of the master regulator, CtrA, by the CIpXP protease is a critical event that enables the initiation of chromosome replication at specific times in the cell cycle. We show here that a previously unidentified single domain-response regulator, CpdR, when in the unphosphorylated state, binds to CIpXP and, thereby, causes its localization to the cell pole. We further show that CIpXP localization is required for CtrA proteolysis. When CpdR is phosphorylated, CIpXP is delocalized, and CtrA is not degraded. Both CtrA and CpdR are phosphorylated via the same CckA histidine kinase phospho-signaling pathway, providing a reinforcing mechanism that simultaneously activates CtrA and prevents its degradation by delocalizing the CpdR/ClpXP complex. In swarmer cells, CpdR is in the phosphorylated state, thus preventing CIpXP localization and CtrA degradation. As swarmer cells differentiate into stalked cells (Gi/S transition), unphosphorylated CpdR accumulates and is localized to the stalked cell pole, where it enables CIpXP localization and CtrA proteolysis, allowing the initiation of DNA replication. Dynamic protease localization mediated by a phosphosignaling pathway is a novel mechanism to integrate spatial and temporal control of bacterial cell cycle progression.