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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001040&type=printable |
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| 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 |
| collection | DOAJ |
| 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 |
| id | doaj-art-573ffac3d9af43d1830496532e96ffb1 |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2010-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-573ffac3d9af43d1830496532e96ffb12025-08-20T02:31:50ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582010-12-01612e100104010.1371/journal.pcbi.1001040Phase-locked signals elucidate circuit architecture of an oscillatory pathway.Andreja JovicBryan HowellMichelle CoteSusan M WadeKhamir MehtaAtsushi MiyawakiRichard R NeubigJennifer J LindermanShuichi TakayamaThis 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001040&type=printable |
| spellingShingle | 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. PLoS Computational Biology |
| title | 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_short | Phase-locked signals elucidate circuit architecture of an oscillatory pathway. |
| title_sort | phase locked signals elucidate circuit architecture of an oscillatory pathway |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001040&type=printable |
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