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

Sören Abel, Peter Chien, Paul Wassmann, Tilman Schirmer, Volkhard Kaever, Michael T. Laub, Tania A. Baker, Urs Jenal

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)550-560
Number of pages11
JournalMolecular cell
Volume43
Issue number4
DOIs
StatePublished - Aug 19 2011

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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