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Coordination of bacterial proteome with metabolism by cyclic AMP signalling.
You, Conghui; Okano, Hiroyuki; Hui, Sheng; Zhang, Zhongge; Kim, Minsu; Gunderson, Carl W; Wang, Yi-Ping; Lenz, Peter; Yan, Dalai; Hwa, Terence.
Afiliação
  • You C; Department of Physics, University of California at San Diego, La Jolla, California 92093-0374, USA.
Nature ; 500(7462): 301-6, 2013 Aug 15.
Article em En | MEDLINE | ID: mdl-23925119
The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Regulação Bacteriana da Expressão Gênica / AMP Cíclico / Proteoma / Proteínas de Escherichia coli / Escherichia coli Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Regulação Bacteriana da Expressão Gênica / AMP Cíclico / Proteoma / Proteínas de Escherichia coli / Escherichia coli Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2013 Tipo de documento: Article