Regulatory Cohesion of Cell Cycle and Cell Differentiation through Interlinked Phosphorylation and Second Messenger Networks

• Published in: Molecular cell Vol. 43; no. 4; pp. 550 - 560
• Main Authors: Abel, Sören, Chien, Peter, Wassmann, Paul, Schirmer, Tilman, Kaever, Volkhard, Laub, Michael T., Baker, Tania A., Jenal, Urs
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19-08-2011
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Proteins - physiology; Caulobacter crescentus; Caulobacter crescentus - cytology; Caulobacter crescentus - metabolism; Caulobacter crescentus - physiology; Cell Cycle - physiology; cell differentiation; Cell Polarity; cohesion; degradation; interphase; metabolism; Models, Biological; morphogenesis; Phosphoric Diester Hydrolases - metabolism; Phosphoric Diester Hydrolases - physiology; Phosphorylation; proteases; protein degradation; proteinases; Second Messenger Systems
• ISSN: 1097-2765; 1097-4164
• 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.
► Coordinate action of the DGCs PleD and DgcB control Caulobacter cell cycle and development ► The PDE PdeA opposes DgcB and thereby determines the swarmer cell-specific program ► Cell cycle-dependent degradation of PdeA releases its antagonist DgcB ► CpdR plays a dual role as protease localization factor and adaptor for PdeA