title: Exponential signaling gain at the receptor level enhances signal-to-noise ratio in bacterial chemotaxis.
abstract: Cellular signaling systems show astonishing precision in their response to external stimuli despite strong fluctuations in the molecular components that determine pathway activity. To control the effects of noise on signaling most efficiently, living cells employ compensatory mechanisms that reach from simple negative feedback loops to robustly designed signaling architectures. Here, we report on a novel control mechanism that allows living cells to keep precision in their signaling characteristics - stationary pathway output, response amplitude, and relaxation time - in the presence of strong intracellular perturbations. The concept relies on the surprising fact that for systems showing perfect adaptation an exponential signal amplification at the receptor level suffices to eliminate slowly varying multiplicative noise. To show this mechanism at work in living systems, we quantified the response dynamics of the E. coli chemotaxis network after genetically perturbing the information flux between upstream and downstream signaling components. We give strong evidence that this signaling system results in dynamic invariance of the activated response regulator against multiplicative intracellular noise. We further demonstrate that for environmental conditions, for which precision in chemosensing is crucial, the invariant response behavior results in highest chemotactic efficiency. Our results resolve several puzzling features of the chemotaxis pathway that are widely conserved across prokaryotes but so far could not be attributed any functional role.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Neumann
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Løvdok
authors.affiliation: Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Kajetan
authors.initials: K
authors.lastname: Bentele
authors.affiliation: Institute for Theoretical Biology, Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Meisig
authors.affiliation: Department of Physics and Institute for Complex Systems and Mathematical Biology (ICSMB), Aberdeen, United Kingdom.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Ullner
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Ferencz S
authors.initials: FS
authors.lastname: Paldy
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Sourjik
authors.affiliation: Department Biologie, Heinrich-Heine-Universität, Düsseldorf, Düsseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kollmann
mesh_terms: D000465:Algorithms; D018407:Bacterial Physiological Phenomena; D002633:Chemotaxis; D004926:Escherichia coli / Q000502:physiology; D008962:Models, Theoretical; D015398:Signal Transduction
references.citation: PLoS Comput Biol. 2011 Nov;7(11):e1002218
references.pmid: 22215991
references.citation: Mol Syst Biol. 2010 Jun 22;6:382
references.pmid: 20571531
references.citation: Science. 2000 Mar 3;287(5458):1652-5
references.pmid: 10698740
references.citation: Nature. 2005 Nov 24;438(7067):504-7
references.pmid: 16306993
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6403-8
references.pmid: 18427119
references.citation: Nature. 1999 Jan 14;397(6715):168-71
references.pmid: 9923680
references.citation: J Biotechnol. 2007 Apr 30;129(2):173-80
references.pmid: 17339063
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1786-91
references.pmid: 16446460
references.citation: Science. 2002 Aug 16;297(5584):1183-6
references.pmid: 12183631
references.citation: J Bacteriol. 2004 Jun;186(12):3687-94
references.pmid: 15175281
references.citation: Science. 2008 Jan 25;319(5862):482-4
references.pmid: 18218902
references.citation: J Biol Chem. 2002 Sep 27;277(39):36755-9
references.pmid: 12119290
references.citation: Cell. 2009 Aug 21;138(4):760-73
references.pmid: 19703401
references.citation: Nature. 2010 Sep 9;467(7312):174-8
references.pmid: 20829788
references.citation: Biochemistry. 1995 Nov 14;34(45):14626-36
references.pmid: 7578071
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13040-4
references.pmid: 16924119
references.citation: Nature. 1997 Jun 26;387(6636):913-7
references.pmid: 9202124
references.citation: Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):123-7
references.pmid: 11742065
references.citation: Mol Syst Biol. 2009;5:238
references.pmid: 19156130
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):691-6
references.pmid: 12522261
references.citation: Nature. 1972 Oct 27;239(5374):500-4
references.pmid: 4563019
references.citation: PLoS Biol. 2009 Aug;7(8):e1000171
references.pmid: 19688030
references.citation: Science. 2010 Sep 24;329(5999):1656-60
references.pmid: 20929850
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15995-6000
references.pmid: 20729472
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4649-53
references.pmid: 10781070
references.citation: Biochemistry. 2000 Oct 31;39(43):13157-65
references.pmid: 11052668
references.citation: Mol Microbiol. 2000 Aug;37(4):740-51
references.pmid: 10972797
references.citation: Phys Rev Lett. 2009 May 29;102(21):218103
references.pmid: 19519139
references.citation: Microbiol Mol Biol Rev. 2004 Jun;68(2):301-19
references.pmid: 15187186
references.citation: Nature. 2004 Mar 25;428(6981):437-41
references.pmid: 15042093
references.citation: Cell. 2011 Apr 15;145(2):312-21
references.pmid: 21496648
references.citation: Cell. 2008 Oct 17;135(2):216-26
references.pmid: 18957198
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17072-7
references.pmid: 15569922
references.citation: Mol Microbiol. 2008 Jun;68(5):1228-36
references.pmid: 18476921
references.citation: Nature. 2000 Jun 1;405(6786):590-3
references.pmid: 10850721
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12669-74
references.pmid: 12232047
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10667-72
references.pmid: 10485883