The Calcium Kinetics and Inositol Trisphosphate Receptor Properties Shape the Asymmetric Timing Window of Coincidence Detection

Ogasawara, Haruhiko

doi:10.1523/jneurosci.0644-08.2008

Cited by 4 publications

(2 citation statements)

References 7 publications

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“…Several studies suggested that the mechanism of synergistic Ca 2+ signaling directly involves PLC activation [10, 12, 16-19, 22-24], and recent studies in macrophages and a macrophage-like cell line argue that synergistic stimulation of Ca 2+ signaling primarily requires the PLC-β3 isoform [10]. However, other work suggested that cellular G i -G q synergism involves interaction between the G proteins [25] or the IP 3 receptor [26], and its biochemical mechanism remained unknown.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Activation of Phospholipase C-β3 by Gαq and Gβγ Describes a Simple Two-State Coincidence Detector

et al. 2010

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Summary Background Receptors that couple to Gi and Gq often interact synergistically in cells to elicit cytosolic Ca2+ transients that are several-fold higher than the sum of those driven by each receptor alone. Such synergism is commonly assumed to be complex, requiring regulatory interaction between components, multiple pathways, or multiple states of the target protein. Results We show that cellular Gi-Gq synergism derives from direct supra-additive stimulation of phospholipase C-β3 (PLC-β3) by G protein subunits Gβγ and Gαq, the relevant components of the Gi and Gq signaling pathways. No additional pathway or proteins are required. Synergism is quantitatively explained by the classical and simple two-state (inactive↔active) allosteric mechanism. We show generally that synergistic activation of a two-state enzyme reflects enhanced conversion to the active state when both ligands are bound, not merely the enhancement of ligand affinity predicted by positive cooperativity. The two-state mechanism also explains why synergism is unique to PLC-β3 among the four PLC-β isoforms and, in general, why one enzyme may respond synergistically to two activators while another does not. Expression of synergism demands that an enzyme display low basal activity in the absence of ligand and becomes significant only when basal activity is ≤ 0.1% of maximal. Conclusions Synergism can be explained by a simple and general mechanism, and such a mechanism sets parameters for its occurrence. Any two-state enzyme is predicted to respond synergistically to multiple activating ligands if, but only if, its basal activity is strongly suppressed.

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Section: Introductionmentioning

confidence: 99%

Synergistic Activation of Phospholipase C-β3 by Gαq and Gβγ Describes a Simple Two-State Coincidence Detector

et al. 2010

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“…In this framework, time within a cellular process can be decoded by examining the pattern of activation of various receptors or cellular pathways. For example, receptors, such as the ionotropic NMDA receptor (Fig 1A [5]) or the IP3 receptor [6], act as coincidence detectors at the neuronal level. Synaptic NMDA-dependent long-term potentiation (LTP), a process thought to underlie learning and memory, requires not just glutamate, but also the removal of the Mg 2+ block as a result of membrane depolarization, usually provided by AMPA receptor currents [7,8]* (Fig 1A).…”

Section: Coincidence Detection: From Receptors To Cellular Processesmentioning

confidence: 99%

Clocks within clocks: timing by coincidence detection

Buhusi

Oprisan

Buhusi

2016

Current Opinion in Behavioral Sciences

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The many existent models of timing rely on vastly different mechanisms to track temporal information. Here we examine these differences, and identify coincidence detection in its most general form as a common mechanism that many apparently different timing models share, as well as a common mechanism of biological circadian, millisecond and interval timing. This view predicts that timing by coincidence detection is a ubiquitous phenomenon at many biological levels, explains the reports of biological timing in many brain areas, explains the role of neural noise at different time scales at both biological and theoretical levels, and provides cohesion within the timing field.

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Computational Models of Cerebellar Long-Term Memory

Ogasawara

Kawato²

2009

Systems Biology

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The Calcium Kinetics and Inositol Trisphosphate Receptor Properties Shape the Asymmetric Timing Window of Coincidence Detection

Cited by 4 publications

References 7 publications

Synergistic Activation of Phospholipase C-β3 by Gαq and Gβγ Describes a Simple Two-State Coincidence Detector

Synergistic Activation of Phospholipase C-β3 by Gαq and Gβγ Describes a Simple Two-State Coincidence Detector

Clocks within clocks: timing by coincidence detection

Computational Models of Cerebellar Long-Term Memory

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