Second messenger-mediated spatiotemporal control of protein degradation regulates bacterial cell cycle progression.
Second messengers control a wide range of important cellular functions in eukaryotes and prokaryotes. Here we show that cyclic di-GMP, a global bacterial second messenger, promotes cell cycle progression in Caulobacter crescentus by mediating the specific degradation of the replication initiation inhibitor CtrA. During the G1-to-S-phase transition, both CtrA and its cognate protease ClpXP dynamically localize to the old cell pole, where CtrA is rapidly degraded. Sequestration of CtrA to the cell pole depends on PopA, a newly identified cyclic di-GMP effector protein. PopA itself localizes to the cell pole and directs CtrA to this subcellular site via the direct interaction with a mediator protein, RcdA. We present evidence that c-di-GMP regulates CtrA degradation during the cell cycle by controlling the dynamic sequestration of the PopA recruitment factor to the cell pole. Furthermore, we show that cell cycle timing of CtrA degradation relies on converging pathways responsible for substrate and protease localization to the old cell pole. This is the first report that links cyclic di-GMP to protein dynamics and cell cycle control in bacteria.
Duerig
Anna
A
Biozentrum, University of Basel, 4056 Basel, Switzerland.
Abel
Sören
S
Folcher
Marc
M
Nicollier
Micael
M
Schwede
Torsten
T
Amiot
Nicolas
N
Giese
Bernd
B
Jenal
Urs
U
D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; C096455:PleD protein, Caulobacter crescentus; D014157:Transcription Factors