scholarly journals Reciprocal Relationship Between Calcium Signaling and Circadian Clocks: Implications for Calcium Homeostasis, Clock Function, and Therapeutics

2021 ◽  
Vol 14 ◽  
Author(s):  
Javier Cavieres-Lepe ◽  
John Ewer
Keyword(s):  
Circadian Clock ◽  
Calcium Signaling ◽  
Calcium Homeostasis ◽  
Reciprocal Relationship ◽  
Circadian Clocks ◽  
Bidirectional Regulation ◽  
Daily Rhythmicity ◽  
External Signals

Graphical AbstractReciprocal relationship between Ca2+ signaling and the circadian clock. In Drosophila and mice, circadian clocks impose a daily rhythmicity to Ca2+ signaling; and, conversely, Ca2+ rhythms and signaling contribute to transmitting daily external signals to the clock TTFL. This bidirectional regulation is critical to the daily rhythmicity of many physiological and behavioral processes.

scholarly journals Genetic redundancy strengthens the circadian clock leading to a narrow entrainment range

2013 ◽  
Vol 10 (84) ◽  
pp. 20130221 ◽  
Author(s):  
A. Erzberger ◽  
G. Hampp ◽  
A. E. Granada ◽  
U. Albrecht ◽  
H. Herzel
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Genetic Network ◽  
Circadian Clocks ◽  
Mutant Mice ◽  
Nonlinear Phenomena ◽  
Genetic Redundancy ◽  
Activity Rhythms ◽  
Almost All ◽  
External Signals

Circadian clocks are internal timekeepers present in almost all organisms. Driven by a genetic network of highly conserved structure, they generate self-sustained oscillations that entrain to periodic external signals such as the 24 h light–dark cycle. Vertebrates possess multiple, functionally overlapping homologues of the core clock genes. Furthermore, vertebrate clocks entrain to a range of periods three times as narrow as that of other organisms. We asked whether genetic redundancies play a role in governing entrainment properties and analysed locomotor activity rhythms of genetically modified mice lacking one set of clock homologues. Exposing them to non-24 h light–dark cycles, we found that the mutant mice have a wider entrainment range than the wild types. Spectral analysis furthermore revealed nonlinear phenomena of periodically forced self-sustained oscillators for which the entrainment range relates inversely to oscillator amplitude. Using the forced oscillator model to explain the observed differences in entrainment range between mutant and wild-type mice, we sought to quantify the overall oscillator amplitude of their clocks from the activity rhythms and found that mutant mice have weaker circadian clocks than wild types. Our results suggest that genetic redundancy strengthens the circadian clock leading to a narrow entrainment range in vertebrates.

scholarly journals The Impact of Vitamin D3Supplementation on Mechanisms of Cell Calcium Signaling in Chronic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ingrid Lajdova ◽  
Viera Spustova ◽  
Adrian Oksa ◽  
Zuzana Kaderjakova ◽  
Dusan Chorvat ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Calcium Signaling ◽  
Calcium Homeostasis ◽  
Calcium Release ◽  
Calcium Entry ◽  
Regulatory Mechanisms ◽  
Cell Calcium ◽  
Crac Channels ◽  
The Impact

Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitaminD3on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000–14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitaminD3supplementation, serum concentration of 25(OH)D3increased (P<0.001) and[Ca2+]idecreased (P<0.001). The differences in[Ca2+]iwere inversely related to differences in 25(OH)D3concentration (P<0.01). VitaminD3supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7channels. The function of P2X7receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitaminD3on P2X7pores and activity of plasma membrane Ca2+-ATPases. VitaminD3supplementation had a beneficial effect on[Ca2+]idecreasing calcium entry via CRAC and P2X7channels and reducing P2X7receptors expression.

Synchronizing the Neurospora crassa circadian clock with the rhythmic environment

2005 ◽  
Vol 33 (5) ◽  
pp. 949-952 ◽  
Author(s):  
N. Price-Lloyd ◽  
M. Elvin ◽  
C. Heintzen
Keyword(s):  
Light Intensity ◽  
Circadian Clock ◽  
Neurospora Crassa ◽  
Model Organism ◽  
Circadian Clocks ◽  
Current Understanding ◽  
Signalling Pathways ◽  
Selection Pressures ◽  
The Earth ◽  
Natural Cycles

The metronomic predictability of the environment has elicited strong selection pressures for the evolution of endogenous circadian clocks. Circadian clocks drive molecular and behavioural rhythms that approximate the 24 h periodicity of our environment. Found almost ubiquitously among phyla, circadian clocks allow preadaptation to rhythms concomitant with the natural cycles of the Earth. Cycles in light intensity and temperature for example act as important cues that couple circadian clocks to the environment via a process called entrainment. This review summarizes our current understanding of the general and molecular principles of entrainment in the model organism Neurospora crassa, a simple eukaryote that has one of the best-studied circadian systems and light-signalling pathways.

scholarly journals Interaction between photoperiod and variation in circadian rhythms in tomato

2022 ◽  
Author(s):  
Yanli Xiang ◽  
Thomas Sapir ◽  
Pauline Rouillard ◽  
Marina Ferrand ◽  
Jose M Jimenez-Gomez
Keyword(s):  
Seasonal Variation ◽  
Circadian Rhythms ◽  
Phase Shift ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Circadian Clocks ◽  
Biological Processes ◽  
Near Isogenic Lines ◽  
Transcriptomic Profiling ◽  
Isogenic Lines

Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust to the time of the year. Modification of circadian clocks is especially relevant in crops to enhance their cultivability in specific regions by changing their sensibility to photoperiod. In tomato, the appearance of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) during domestication delayed its circadian rhythms, and allowed its expansion outside its equatorial origin. Here we study how variation in circadian rhythms in tomato affects its perception of photoperiod. To do this, we create near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and perform transcriptomic profiling under two different photoperiods. We observe that EID1, but not LNK2, has a large effect on the tomato transcriptome and its response to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.

scholarly journals Peripheral Sensory Organs Contribute to Temperature Synchronization of the Circadian Clock in Drosophila melanogaster

2021 ◽  
Vol 12 ◽  
Author(s):  
Rebekah George ◽  
Ralf Stanewsky
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Circadian Clock ◽  
Temperature Fluctuations ◽  
Fruit Fly ◽  
Circadian Clocks ◽  
Sensory Cells ◽  
Clock Gene Expression ◽  
External Time ◽  
Peripheral Sensory

Circadian clocks are cell-autonomous endogenous oscillators, generated and maintained by self-sustained 24-h rhythms of clock gene expression. In the fruit fly Drosophila melanogaster, these daily rhythms of gene expression regulate the activity of approximately 150 clock neurons in the fly brain, which are responsible for driving the daily rest/activity cycles of these insects. Despite their endogenous character, circadian clocks communicate with the environment in order to synchronize their self-sustained molecular oscillations and neuronal activity rhythms (internal time) with the daily changes of light and temperature dictated by the Earth’s rotation around its axis (external time). Light and temperature changes are reliable time cues (Zeitgeber) used by many organisms to synchronize their circadian clock to the external time. In Drosophila, both light and temperature fluctuations robustly synchronize the circadian clock in the absence of the other Zeitgeber. The complex mechanisms for synchronization to the daily light–dark cycles are understood with impressive detail. In contrast, our knowledge about how the daily temperature fluctuations synchronize the fly clock is rather limited. Whereas light synchronization relies on peripheral and clock-cell autonomous photoreceptors, temperature input to the clock appears to rely mainly on sensory cells located in the peripheral nervous system of the fly. Recent studies suggest that sensory structures located in body and head appendages are able to detect temperature fluctuations and to signal this information to the brain clock. This review will summarize these studies and their implications about the mechanisms underlying temperature synchronization.

scholarly journals The Circadian Clock, the Brain, and COVID-19: The Cases of Olfaction and the Timing of Sleep

2021 ◽  
pp. 074873042110312
Author(s):  
Rachel S. Herz ◽  
Erik D. Herzog ◽  
Martha Merrow ◽  
Sara B. Noya
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Function ◽  
Human Brain ◽  
Circadian Clock ◽  
Clinical Data ◽  
Circadian Clocks ◽  
Olfactory Sensitivity ◽  
Daily Rhythms ◽  
Sense Of Smell ◽  
The Brain

Daily rhythms of behavior and neurophysiology are integral to the circadian clocks of all animals. Examples of circadian clock regulation in the human brain include daily rhythms in sleep-wake, cognitive function, olfactory sensitivity, and risk for ischemic stroke, all of which overlap with symptoms displayed by many COVID-19 patients. Motivated by the relatively unexplored, yet pervasive, overlap between circadian functions and COVID-19 neurological symptoms, this perspective piece uses daily variations in the sense of smell and the timing of sleep and wakefulness as illustrative examples. We propose that time-stamping clinical data and testing may expand and refine diagnosis and treatment of COVID-19.

scholarly journals CikA, an Input Pathway Component, Senses the Oxidized Quinone Signal to Generate Phase Delays in the Cyanobacterial Circadian Clock

2020 ◽  
Vol 35 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Pyonghwa Kim ◽  
Brianna Porr ◽  
Tetsuya Mori ◽  
Yong-Sung Kim ◽  
Carl H. Johnson ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Time Of Day ◽  
Fine Tuning ◽  
Circadian Oscillation ◽  
Clock Proteins ◽  
Entrainment Process ◽  
Central Oscillator ◽  
External Signals ◽  
Full Synchronization

The circadian clock is a timekeeping system in most organisms that keeps track of the time of day. The rhythm generated by the circadian oscillator must be constantly synchronized with the environmental day/night cycle to make the timekeeping system truly advantageous. In the cyanobacterial circadian clock, quinone is a biological signaling molecule used for entraining and fine-tuning the oscillator, a process in which the external signals are transduced into biological metabolites that adjust the phase of the circadian oscillation. Among the clock proteins, the pseudo-receiver domain of KaiA and CikA can sense external cues by detecting the oxidation state of quinone, a metabolite that reflects the light/dark cycle, although the molecular mechanism is not fully understood. Here, we show the antagonistic phase shifts produced by the quinone sensing of KaiA and CikA. We introduced a new cyanobacterial circadian clock mixture that includes an input component in vitro. KaiA and CikA cause phase advances and delays, respectively, in this circadian clock mixture in response to the quinone signal. In the entrainment process, oxidized quinone modulates the functions of KaiA and CikA, which dominate alternatively at day and night in the cell. This in turn changes the phosphorylation state of KaiC—the central oscillator in cyanobacteria—ensuring full synchronization of the circadian clock. Moreover, we reemphasize the mechanistic input functionality of CikA, contrary to other reports that focus only on its output action.

scholarly journals Computational modelling unravels the precise clockwork of cyanobacteria

2018 ◽  
Vol 8 (6) ◽  
pp. 20180038 ◽  
Author(s):  
Nicolas M. Schmelling ◽  
Ilka M. Axmann
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Circadian Clock ◽  
Environmental Changes ◽  
Regulation Of Gene Expression ◽  
Computational Modelling ◽  
Circadian Clocks ◽  
Fitness Advantage ◽  
Fundamental Part ◽  
Global Gene Regulation

Precisely timing the regulation of gene expression by anticipating recurring environmental changes is a fundamental part of global gene regulation. Circadian clocks are one form of this regulation, which is found in both eukaryotes and prokaryotes, providing a fitness advantage for these organisms. Whereas many different eukaryotic groups harbour circadian clocks, cyanobacteria are the only known oxygenic phototrophic prokaryotes to regulate large parts of their genes in a circadian fashion. A decade of intensive research on the mechanisms and functionality using computational and mathematical approaches in addition to the detailed biochemical and biophysical understanding make this the best understood circadian clock. Here, we summarize the findings and insights into various parts of the cyanobacterial circadian clock made by mathematical modelling. These findings have implications for eukaryotic circadian research as well as synthetic biology harnessing the power and efficiency of global gene regulation.

PREMONition: An algorithm for predicting the circadian clock-regulated molecular network

2018 ◽  
Author(s):  
Jasper Bosman ◽  
Zheng Eelderink-Chen ◽  
Emma Laing ◽  
Martha Merrow
Keyword(s):  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Circadian Clocks ◽  
Model Systems ◽  
Functional Relationships ◽  
Growth Assay ◽  
Living Organisms ◽  
Clock Mechanism ◽  
Transcriptional Feedback

AbstractA transcriptional feedback loop is central to clock function in animals, plants and fungi. The clock genes involved in its regulation are specific to - and highly conserved within - the kingdoms of life. However, other shared clock mechanisms, such as phosphorylation, are mediated by proteins found broadly among living organisms, performing functions in many cellular sub-systems. Use of homology to directly infer involvement/association with the clock mechanism in new, developing model systems, is therefore of limited use. Here we describe the approach PREMONition,PREdictingMolecularNetworks, that uses functional relationships to predict molecular circadian clock associations. PREMONition is based on the incorporation of proteins encoded by known clock genes (when available), rhythmically expressed clock-controlled genes and non-rhythmically expressed but interacting genes into a cohesive network. After tuning PREMONition on the networks derived for human, fly and fungal circadian clocks, we deployed the approach to predict a molecular clock network forSaccharomyces cerevisiae, for which there are no readily-identifiable clock gene homologs. The predicted network was validated using gene expression data and a growth assay for sensitivity to light, a zeitgeber of circadian clocks of most organisms. PREMONition may be used to identify candidate clock-regulated processes and thus candidate clock genes in other organisms.

scholarly journals Metabolite-mediated TOR signaling regulates the circadian clock inArabidopsis

2019 ◽  
Vol 116 (51) ◽  
pp. 25395-25397 ◽  
Author(s):  
Nan Zhang ◽  
Yanyan Meng ◽  
Xu Li ◽  
Yu Zhou ◽  
Liuyin Ma ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Circadian Clocks ◽  
Circadian Period ◽  
Energy Status ◽  
Vitamin B3 ◽  
Tor Signaling ◽  
Energy Sensor ◽  
Tor Kinase ◽  
Effect Of Glucose ◽  
Kinase A

Circadian clocks usually run with a period close to 24 h, but are also plastic and can be entrained by external environmental conditions and internal physiological cues. Two key nutrient metabolites, glucose and vitamin B3 (nicotinamide), can influence the circadian period in both mammals and plants; however, the underlying molecular mechanism is still largely unclear. We reveal that the target of rapamycin (TOR) kinase, a conserved central growth regulator, is essential for glucose- and nicotinamide-mediated control of the circadian period inArabidopsis. Nicotinamide affects the cytosolic adenosine triphosphate concentration, and blocks the effect of glucose-TOR energy signaling on period length adjustment, meristem activation, and root growth. Together, our results uncover a missing link between cellular metabolites, energy status, and circadian period adjustment, and identify TOR kinase as an essential energy sensor to coordinate circadian clock and plant growth.

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