Signalling network with a bistable hysteretic switch controls developmental activation of the σF transcription factor in Bacillus subtilis

Oleg A. Igoshin, Chester W. Price, Michael A. Savageau

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The sporulation process of the bacterium Bacillus subtilis unfolds by means of separate but co-ordinated programmes of gene expression within two unequal cell compartments, the mother cell and the smaller forespore. σF is the first compartment-specific transcription factor activated during this process, and it is controlled at the post-translational level by a partner-switching mechanism that restricts σF activity to the forespore. The crux of this mechanism lies in the ability of the anti-sigma factor SpoIIAB (AB) to form alternative complexes either with σF, holding it in an inactive form, or with the anti-anti-sigma factor SpoIIAA (AA) and a nucleotide, either ATP or ADP. In the complex with AB and ATP, AA is phosphorylated on a serine residue and released, making AB available to capture σF in an inactive complex. Subsequent activation of σF requires the intervention of the SpoIIE serine phosphatase to dephosphorylate AA, which can then attack the AB-σF complex to induce the release of σF. By incorporating biochemical, biophysical and genetic data from the literature we have constructed an integrative mathematical model of this partner-switching network. The model predicts that the self-enhancing formation of a long-lived complex of AA, AB and ADP transforms the network into an essentially irreversible hysteretic switch, thereby explaining the sharp, robust and irreversible activation of σF in the forespore compartment. The model also clarifies the contributions of the partly redundant mechanisms that ensure correct spatial and temporal activation of σF, reproduces the behaviour of various mutants and makes strong, testable predictions.

Original languageEnglish (US)
Pages (from-to)165-184
Number of pages20
JournalMolecular Microbiology
Volume61
Issue number1
DOIs
StatePublished - Jul 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

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