title: Slowdown of growth controls cellular differentiation.
abstract: How can changes in growth rate affect the regulatory networks behavior and the outcomes of cellular differentiation? We address this question by focusing on starvation response in sporulating Bacillus subtilis We show that the activity of sporulation master regulator Spo0A increases with decreasing cellular growth rate. Using a mathematical model of the phosphorelay-the network controlling Spo0A-we predict that this increase in Spo0A activity can be explained by the phosphorelay protein accumulation and lengthening of the period between chromosomal replication events caused by growth slowdown. As a result, only cells growing slower than a certain rate reach threshold Spo0A activity necessary for sporulation. This growth threshold model accurately predicts cell fates and explains the distribution of sporulation deferral times. We confirm our predictions experimentally and show that the concentration rather than activity of phosphorelay proteins is affected by the growth slowdown. We conclude that sensing the growth rates enables cells to indirectly detect starvation without the need for evaluating specific stress signals.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Jatin
authors.initials: J
authors.lastname: Narula
authors.affiliation: Division of Biological Sciences, UCSD, San Diego, CA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuchina
authors.affiliation: Division of Biological Sciences, UCSD, San Diego, CA, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Division of Biological Sciences, UCSD, San Diego, CA, USA.
authors.forename: Gürol M
authors.initials: GM
authors.lastname: Süel
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA igoshin@rice.edu.
authors.forename: Oleg A
authors.identifier: 0000-0002-1449-4772
authors.initials: OA
authors.lastname: Igoshin
mesh_terms: D001412:Bacillus subtilis / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D002876:Chromosomes, Bacterial / Q000235:genetics; D003470:Culture Media / Q000737:chemistry; D015964:Gene Expression Regulation, Bacterial; D008962:Models, Theoretical; D013171:Spores, Bacterial / Q000254:growth & development*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; C080950:Spo0A protein, Bacillus subtilis; D014157:Transcription Factors
keywords: B. subtilis; phosphorelay; signal integration