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High-specificity local and global c-di-GMP signaling

Journal

TRENDS IN MICROBIOLOGY
Volume 29, Issue 11, Pages 993-1003

Publisher

CELL PRESS
DOI: 10.1016/j.tim.2021.02.003

Keywords

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Funding

  1. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [He1556/20-1]
  2. DFG [1556/21-1, 1556/21-2]

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Bacteria use a combination of local and global c-di-GMP signaling to create a complex signaling network, allowing for specific parallel pathways. Local c-di-GMP signaling is defined by specific knockout phenotypes, direct protein interactions, and cellular c-di-GMP levels remaining below a certain threshold. Adaptive changes in signaling network architecture can further enhance signaling flexibility.
The striking multiplicity, signal input diversity, and output specificity of c-di-GMP signaling proteins in many bacteria has brought second messenger signaling back onto the agenda of contemporary microbiology. How can several signaling pathways act in parallel in a specific manner if all of them use the same diffusible second messenger present at a certain global cellular concentration? Recent research has now shown that bacteria achieve this by flexibly combining modes of local and global c-di-GMP signaling in complex signaling networks. Three criteria have to be met to define local c-di-GMP signaling: specific knockout phenotypes, direct interactions between proteins involved, and actual cellular c-di-GMP levels remaining below the K-d of effectors. Adaptive changes in signaling network architecture can further enhance signaling flexibility.

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