The evolutionary conservation of eukaryotic membrane-bound adenylyl cyclase isoforms

Schultz, Joachim E.

doi:10.3389/fphar.2022.1009797

Cited by 6 publications

(2 citation statements)

References 56 publications

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“…The channels’ activity is tightly coupled to oscillations in concentrations of specific intracellular messengers like Ca 2+ or cAMP ( Craven and Zagotta, 2006 ; Biel and Michalakis, 2009 ; Johnstone et al, 2018 ; Stengl and Schröder, 2021 ). The Ca 2+ oscillations in turn interlink with endogenous cAMP oscillations, e.g., via Ca 2+ -dependent adenylyl cyclases, or vice versa via cAMP-dependent Ca 2+ permeable ion channels ( Biel and Michalakis, 2009 ; Islam, 2020 ; Schultz, 2022 ; Li et al, 2023a ). Via different intracellular messenger cascades multiscale membrane-associated oscillations link to multiscale TTFL oscillators/clocks engaged in gene regulation networks ( Colwell, 2011 ; Patton et al, 2016 ; Stengl and Arendt, 2016 ; Hastings et al, 2019 ; Perfitt et al, 2020 ; Steven et al, 2020 ; Stengl and Schröder, 2021 ).…”

Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookmentioning

confidence: 99%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl,

Schneider

2024

Front. Physiol.

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Environmental rhythms such as the daily light-dark cycle selected for endogenous clocks. These clocks predict regular environmental changes and provide the basis for well-timed adaptive homeostasis in physiology and behavior of organisms. Endogenous clocks are oscillators that are based on positive feedforward and negative feedback loops. They generate stable rhythms even under constant conditions. Since even weak interactions between oscillators allow for autonomous synchronization, coupling/synchronization of oscillators provides the basis of self-organized physiological timing. Amongst the most thoroughly researched clocks are the endogenous circadian clock neurons in mammals and insects. They comprise nuclear clockworks of transcriptional/translational feedback loops (TTFL) that generate ∼24 h rhythms in clock gene expression entrained to the environmental day-night cycle. It is generally assumed that this TTFL clockwork drives all circadian oscillations within and between clock cells, being the basis of any circadian rhythm in physiology and behavior of organisms. Instead of the current gene-based hierarchical clock model we provide here a systems view of timing. We suggest that a coupled system of autonomous TTFL and posttranslational feedback loop (PTFL) oscillators/clocks that run at multiple timescales governs adaptive, dynamic homeostasis of physiology and behavior. We focus on mammalian and insect neurons as endogenous oscillators at multiple timescales. We suggest that neuronal plasma membrane-associated signalosomes constitute specific autonomous PTFL clocks that generate localized but interlinked oscillations of membrane potential and intracellular messengers with specific endogenous frequencies. In each clock neuron multiscale interactions of TTFL and PTFL oscillators/clocks form a temporally structured oscillatory network with a common complex frequency-band comprising superimposed multiscale oscillations. Coupling between oscillator/clock neurons provides the next level of complexity of an oscillatory network. This systemic dynamic network of molecular and cellular oscillators/clocks is suggested to form the basis of any physiological homeostasis that cycles through dynamic homeostatic setpoints with a characteristic frequency-band as hallmark. We propose that mechanisms of homeostatic plasticity maintain the stability of these dynamic setpoints, whereas Hebbian plasticity enables switching between setpoints via coupling factors, like biogenic amines and/or neuropeptides. They reprogram the network to a new common frequency, a new dynamic setpoint. Our novel hypothesis is up for experimental challenge.

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Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookmentioning

confidence: 99%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl,

Schneider

2024

Front. Physiol.

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“…The Ca 2+ oscillations in turn interlink with endogenous cAMP oscillations, e.g. via Ca 2+ -dependent adenylyl cyclases, or vice versa via cAMP-dependent Ca 2+ permeable ion channels (Biel and Michalakis, 2009;Islam, 2020;Schultz, 2022;Li et al, 2023a). Via different intracellular messenger cascades multiscale membrane-associated oscillations link to multiscale TTFL oscillators/clocks engaged in gene regulation networks (Colwell, 2011;Patton et al, 2016;Stengl and Arendt, 2016;Hastings et al, 2019;Perfitt et al, 2020;Steven et al, 2020;Stengl and Schröder, 2021).…”

Section: Discussion: Our Novel Hypothesis Final Conclusion and Outlookmentioning

confidence: 99%

Contribution of membrane-associated oscillators to biological timing at different timescales

Stengl¹,

Schneider²

2023

Preprint

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Environmental rhythms have selected for endogenous clocks that predict regular environmental changes like the daily light-dark cycle. Endogenous clocks are based on positive feedforward and negative feedback loops that generate rhythms even under constant conditions. Autonomous coupling of oscillators is the basis of self-organized timing that determines the repetitive sequence of events of physiology and behavior while mechanisms of homeostatic plasticity serve to maintain and stabilize physiological and behavioral homeostasis. The best studied biological clocks are circadian clock neurons of insects and mammals. Their molecular clockwork in the nucleus consists of transcriptional and translational feedback loops (TTFLs). This clockwork generates ~24 h rhythms in clock gene expression entrained to the light-dark cycle. It is assumed to drive all circadian oscillations in clock neurons such as rhythms in membrane potential, second messenger levels, and neurotransmitter release, thereby controlling circadian rhythms in physiology and behavior. It is not discerned yet whether the membrane-bound rhythms are mere outputs of the TTFL clockwork or whether instead they are driven by an autonomous posttranscriptional feedback loop (PTFL) clockwork in the plasma membrane. Furthermore, next to circadian rhythms the plasma membrane generates rhythms on much faster or slower timescales. It is not understood whether and how these multiscale rhythms are linked. Based on our work in peripheral and central insect multiscale clock neurons, we hypothesize that the excitable plasma membrane constitutes an adaptive endogenous PTFL clockwork at multiple timescales. Multiscale membrane-associated rhythms are suggested to be coupled to, but not driven by, the TTFL clockwork in the nucleus. Furthermore, we suggest that negative feedback loops via protein kinases and phosphatases on the one hand provide for mechanisms of homeostatic plasticity that maintain physiological homeostasis, keeping the period of cellular clocks stable. On the other hand, they also serve as coupling factors and links between cellular oscillators and clocks at multiple time scales controlling the temporal sequence and/or synchronization of physiological and behavioral processes. Our novel hypothesis is up for challenge in future experiments in different species.

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Heme b inhibits class III adenylyl cyclases

Elsabbagh

Landau

Gross

et al. 2023

Cellular Signalling

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The evolutionary conservation of eukaryotic membrane-bound adenylyl cyclase isoforms

Cited by 6 publications

References 56 publications

Contribution of membrane-associated oscillators to biological timing at different timescales

Contribution of membrane-associated oscillators to biological timing at different timescales

Contribution of membrane-associated oscillators to biological timing at different timescales

Heme b inhibits class III adenylyl cyclases

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