title: Queueing up for enzymatic processing: correlated signaling through coupled degradation.
abstract: High-throughput technologies have led to the generation of complex wiring diagrams as a post-sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how 'waiting lines' can lead to correlations between protein 'customers' that are coupled solely through a downstream set of enzymatic 'servers'. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross-talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post-translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links.
authors.affiliation: Molecular Biology Section, Division of Biological Science, University of California, San Diego, CA, USA.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Cookson
authors.forename: William H
authors.initials: WH
authors.lastname: Mather
authors.forename: Tal
authors.initials: T
authors.lastname: Danino
authors.forename: Octavio
authors.initials: O
authors.lastname: Mondragón-Palomino
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Williams
authors.forename: Lev S
authors.initials: LS
authors.lastname: Tsimring
authors.forename: Jeff
authors.initials: J
authors.lastname: Hasty
mesh_terms: D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D059748:Proteolysis; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology; D049490:Systems Biology
chemical_list: D029968:Escherichia coli Proteins; C483573:ClpXP protease, E coli; D049071:Endopeptidase Clp