Dynamics of two Phosphorelays controlling cell cycle progression in Caulobacter crescentus.
In Caulobacter crescentus, progression through the cell cycle is governed by the periodic activation and inactivation of the master regulator CtrA. Two phosphorelays, each initiating with the histidine kinase CckA, promote CtrA activation by driving its phosphorylation and by inactivating its proteolysis. Here, we examined whether the CckA phosphorelays also influence the downregulation of CtrA. We demonstrate that CckA is bifunctional, capable of acting as either a kinase or phosphatase to drive the activation or inactivation, respectively, of CtrA. By identifying mutations that uncouple these two activities, we show that CckA's phosphatase activity is important for downregulating CtrA prior to DNA replication initiation in vivo but that other phosphatases may exist. Our results demonstrate that cell cycle transitions in Caulobacter require and are likely driven by the toggling of CckA between its kinase and phosphatase states. More generally, our results emphasize how the bifunctional nature of histidine kinases can help switch cells between mutually exclusive states.
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Y Erin
YE
Chen
Christos G
CG
Tsokos
Emanuele G
EG
Biondi
Barrett S
BS
Perchuk
Michael T
MT
Laub
D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000502:physiology*; D002453:Cell Cycle; D004252:DNA Mutational Analysis; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D000071677:Histidine Kinase; D010744:Phosphoric Monoester Hydrolases