Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 3, Pages 1052-1057Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1015397108
Keywords
cellular asymmetry; spatial gradients; two-component signaling; reaction-diffusion model; histidine kinase
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Funding
- National Institutes of Health (NIH) [5R01GM082899, DP2OD006466]
- German Research Foundation
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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 uniformprotein abundance may belie gradients and other sophisticated spatial patterns of protein activity in bacterial cells.
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