title: Regulatory cohesion of cell cycle and cell differentiation through interlinked phosphorylation and second messenger networks.
abstract: 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.
authors.affiliation: Biozentrum of the University of Basel, Klingelbergstrasse 50, CH-4054 Basel, Switzerland.
authors.forename: Sören
authors.initials: S
authors.lastname: Abel
authors.forename: Peter
authors.initials: P
authors.lastname: Chien
authors.forename: Paul
authors.initials: P
authors.lastname: Wassmann
authors.forename: Tilman
authors.initials: T
authors.lastname: Schirmer
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.forename: Michael T
authors.initials: MT
authors.lastname: Laub
authors.forename: Tania A
authors.initials: TA
authors.lastname: Baker
authors.forename: Urs
authors.initials: U
authors.lastname: Jenal
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016935:Caulobacter crescentus / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D016764:Cell Polarity; D008954:Models, Biological; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D015290:Second Messenger Systems
chemical_list: D001426:Bacterial Proteins; C096455:PleD protein, Caulobacter crescentus; D010727:Phosphoric Diester Hydrolases