A cell cycle kinase with tandem sensory PAS domains integrates cell fate cues.
All cells must integrate sensory information to coordinate developmental events in space and time. The bacterium Caulobacter crescentus uses two-component phospho-signalling to regulate spatially distinct cell cycle events through the master regulator CtrA. Here, we report that CckA, the histidine kinase upstream of CtrA, employs a tandem-PAS domain sensor to integrate two distinct spatiotemporal signals. Using CckA reconstituted on liposomes, we show that one PAS domain modulates kinase activity in a CckA density-dependent manner, mimicking the stimulation of CckA kinase activity that occurs on its transition from diffuse to densely packed at the cell poles. The second PAS domain interacts with the asymmetrically partitioned second messenger cyclic-di-GMP, inhibiting kinase activity while stimulating phosphatase activity, consistent with the selective inactivation of CtrA in the incipient stalked cell compartment. The integration of these spatially and temporally regulated signalling events within a single signalling receptor enables robust orchestration of cell-type-specific gene regulation.
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.|Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305, USA.
Thomas H
TH
Mann
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
W
W
Seth Childers
Department of Chemistry, Williams College, Williamstown, Massachusetts 01267, USA.
Jimmy A
JA
Blair
Stanford Protein and Nucleic Acid Facility, Beckman Center, Stanford University School of Medicine, Stanford, California 94305, USA.
Michael R
MR
Eckart
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Lucy
L
Shapiro
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D016935:Caulobacter crescentus / Q000201:enzymology* / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D000071677:Histidine Kinase