Phase-locked signals elucidate circuit architecture of an oscillatory pathway.

This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances,...

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Autores principales:	Andreja Jovic, Bryan Howell, Michelle Cote, Susan M Wade, Khamir Mehta, Atsushi Miyawaki, Richard R Neubig, Jennifer J Linderman, Shuichi Takayama
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/573ffac3d9af43d1830496532e96ffb1
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spelling	oai:doaj.org-article:573ffac3d9af43d1830496532e96ffb12021-11-18T05:50:48ZPhase-locked signals elucidate circuit architecture of an oscillatory pathway.1553-734X1553-735810.1371/journal.pcbi.1001040https://doaj.org/article/573ffac3d9af43d1830496532e96ffb12010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21203481/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances, the number of responses can be fewer than the number of inputs, indicative of skipped beats. While the observation of phase-locking alone is largely independent of detailed mechanism, we find that the properties of phase-locking are useful for discriminating circuit architectures because they reflect not only the activation but also the recovery characteristics of biochemical circuits. Here, this principle is demonstrated for analysis of a G-protein coupled receptor system, the M3 muscarinic receptor-calcium signaling pathway, using microfluidic-mediated periodic chemical stimulation of the M3 receptor with carbachol and real-time imaging of resulting calcium transients. Using this approach we uncovered the potential importance of basal IP3 production, a finding that has important implications on calcium response fidelity to periodic stimulation. Based upon our analysis, we also negated the notion that the Gq-PLC interaction is switch-like, which has a strong influence upon how extracellular signals are filtered and interpreted downstream. Phase-locking analysis is a new and useful tool for model revision and mechanism elucidation; the method complements conventional genetic and chemical tools for analysis of cellular signaling circuitry and should be broadly applicable to other oscillatory pathways.Andreja JovicBryan HowellMichelle CoteSusan M WadeKhamir MehtaAtsushi MiyawakiRichard R NeubigJennifer J LindermanShuichi TakayamaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 12, p e1001040 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andreja Jovic Bryan Howell Michelle Cote Susan M Wade Khamir Mehta Atsushi Miyawaki Richard R Neubig Jennifer J Linderman Shuichi Takayama Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
description	This paper introduces the concept of phase-locking analysis of oscillatory cellular signaling systems to elucidate biochemical circuit architecture. Phase-locking is a physical phenomenon that refers to a response mode in which system output is synchronized to a periodic stimulus; in some instances, the number of responses can be fewer than the number of inputs, indicative of skipped beats. While the observation of phase-locking alone is largely independent of detailed mechanism, we find that the properties of phase-locking are useful for discriminating circuit architectures because they reflect not only the activation but also the recovery characteristics of biochemical circuits. Here, this principle is demonstrated for analysis of a G-protein coupled receptor system, the M3 muscarinic receptor-calcium signaling pathway, using microfluidic-mediated periodic chemical stimulation of the M3 receptor with carbachol and real-time imaging of resulting calcium transients. Using this approach we uncovered the potential importance of basal IP3 production, a finding that has important implications on calcium response fidelity to periodic stimulation. Based upon our analysis, we also negated the notion that the Gq-PLC interaction is switch-like, which has a strong influence upon how extracellular signals are filtered and interpreted downstream. Phase-locking analysis is a new and useful tool for model revision and mechanism elucidation; the method complements conventional genetic and chemical tools for analysis of cellular signaling circuitry and should be broadly applicable to other oscillatory pathways.
format	article
author	Andreja Jovic Bryan Howell Michelle Cote Susan M Wade Khamir Mehta Atsushi Miyawaki Richard R Neubig Jennifer J Linderman Shuichi Takayama
author_facet	Andreja Jovic Bryan Howell Michelle Cote Susan M Wade Khamir Mehta Atsushi Miyawaki Richard R Neubig Jennifer J Linderman Shuichi Takayama
author_sort	Andreja Jovic
title	Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
title_short	Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
title_full	Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
title_fullStr	Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
title_full_unstemmed	Phase-locked signals elucidate circuit architecture of an oscillatory pathway.
title_sort	phase-locked signals elucidate circuit architecture of an oscillatory pathway.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/573ffac3d9af43d1830496532e96ffb1
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Phase-locked signals elucidate circuit architecture of an oscillatory pathway.

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