title: Spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium.
abstract: Spatial asymmetry is crucial to development. One mechanism for generating asymmetry involves the localized synthesis of a key regulatory protein that diffuses away from its source, forming a spatial gradient. Although gradients are prevalent in eukaryotes, at both the tissue and intracellular levels, it is unclear whether gradients of freely diffusible proteins can form within bacterial cells given their small size and the speed of diffusion. Here, we show that the bacterium Caulobacter crescentus generates a gradient of the active, phosphorylated form of the master regulator CtrA, which directly regulates DNA replication. Using a combination of mathematical modeling, single-cell microscopy, and genetic manipulation, we demonstrate that this gradient is produced by the polarly localized phosphorylation and dephosphorylation of CtrA. Our data indicate that cells robustly establish the asymmetric fates of daughter cells before cell division causes physical compartmentalization. More generally, our results demonstrate that uniform protein abundance may belie gradients and other sophisticated spatial patterns of protein activity in bacterial cells.
authors.affiliation: Department of Biology and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Y Erin
authors.initials: YE
authors.lastname: Chen
authors.forename: Carolina
authors.initials: C
authors.lastname: Tropini
authors.forename: Kristina
authors.initials: K
authors.lastname: Jonas
authors.forename: Christos G
authors.initials: CG
authors.lastname: Tsokos
authors.forename: Kerwyn C
authors.initials: KC
authors.lastname: Huang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Laub
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000378:metabolism* / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D036681:Fluorescence Recovery After Photobleaching; D008390:Markov Chains; D008954:Models, Biological; D009010:Monte Carlo Method; D010766:Phosphorylation; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; D014157:Transcription Factors