Biozentrum of the University of Basel, Klingelbergstrasse 50, CH-4054 Basel, Switzerland.
Mol Cell. 2011 Aug 19;43(4):550-60. doi: 10.1016/j.molcel.2011.07.018.
In Caulobacter crescentus, phosphorylation of key regulators is coordinated with the second messenger cyclic di-GMP to drive cell-cycle progression and differentiation. The diguanylate cyclase PleD directs pole morphogenesis, while the c-di-GMP effector PopA initiates degradation of the replication inhibitor CtrA by the AAA+ protease ClpXP to license S phase entry. Here, we establish a direct link between PleD and PopA reliant on the phosphodiesterase PdeA and the diguanylate cyclase DgcB. PdeA antagonizes DgcB activity until the G1-S transition, when PdeA is degraded by the ClpXP protease. The unopposed DgcB activity, together with PleD activation, upshifts c-di-GMP to drive PopA-dependent CtrA degradation and S phase entry. PdeA degradation requires CpdR, a response regulator that delivers PdeA to the ClpXP protease in a phosphorylation-dependent manner. Thus, CpdR serves as a crucial link between phosphorylation pathways and c-di-GMP metabolism to mediate protein degradation events that irreversibly and coordinately drive bacterial cell-cycle progression and development.
在新月柄杆菌中，关键调控蛋白的磷酸化与第二信使环二鸟苷酸（c-di-GMP）协同作用，驱动细胞周期的进行和分化。双鸟苷酸环化酶 PleD 指导菌毛的形态发生，而 c-di-GMP 效应物 PopA 通过 AAA+蛋白酶 ClpXP 引发复制抑制剂 CtrA 的降解，以启动 S 期进入。在这里，我们建立了 PleD 和 PopA 之间的直接联系，这依赖于磷酸二酯酶 PdeA 和双鸟苷酸环化酶 DgcB。PdeA 拮抗 DgcB 的活性，直到 G1-S 转换期，此时 PdeA 被 ClpXP 蛋白酶降解。无拮抗的 DgcB 活性，加上 PleD 的激活，使 c-di-GMP 升高，从而驱动 PopA 依赖性的 CtrA 降解和 S 期进入。PdeA 的降解需要 CpdR，这是一种响应调节因子，它以依赖于磷酸化的方式将 PdeA 递送给 ClpXP 蛋白酶。因此，CpdR 是磷酸化途径和 c-di-GMP 代谢之间的关键联系，介导不可逆和协调的蛋白质降解事件，从而推动细菌细胞周期的进行和发育。
