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 DOUBLETIME Plays a Noncatalytic Role To Mediate CLOCK Phosphorylation and Repress CLOCK-Dependent Transcription within the Drosophila Circadian Clock

2009 ◽  
Vol 29 (6) ◽  
pp. 1452-1458 ◽  
Author(s):  
Wangjie Yu ◽  
Hao Zheng ◽  
Jeffrey L. Price ◽  
Paul E. Hardin
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Catalytic Activity ◽  
Circadian Clock ◽  
Transcriptional Repression ◽  
Protein Complexes ◽  
Time Of Day ◽  
Feedback Loops ◽  
Circadian Clocks ◽  
Synthesis Activity

ABSTRACT Circadian clocks keep time via gene expression feedback loops that are controlled by time-of-day-specific changes in the synthesis, activity, and degradation of transcription factors. Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a transcriptional repressor, and CLOCK (CLK), a transcriptional activator, as CLK-dependent transcription is being repressed. PER- and DBT-containing protein complexes feed back to repress CLK-dependent transcription, but how DBT promotes PER and CLK phosphorylation and how PER and CLK phosphorylation contributes to transcriptional repression have not been defined. Here, we show that DBT catalytic activity is not required for CLK phosphorylation or transcriptional repression and that PER phosphorylation is dispensable for repressing CLK-dependent transcription. These results support a model in which DBT plays a novel noncatalytic role in recruiting additional kinases that phosphorylate CLK, thereby repressing transcription. A similar mechanism likely operates in mammals, given the conserved activities of PER, DBT, and CLK orthologs.

scholarly journals Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery

2020 ◽  
Vol 48 (14) ◽  
pp. 7944-7957
Author(s):  
Renbin Lu ◽  
Yufan Dong ◽  
Jia-Da Li
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Clock Gene ◽  
Ubiquitin Proteasome System ◽  
Circadian Clocks ◽  
Clock Gene Expression ◽  
Ubiquitin Proteasome ◽  
Hsp90 Chaperone ◽  
Abnormal Behaviors ◽  
Clock Protein

Abstract Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin–proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.

scholarly journals The Effect of General Anaesthesia on Circadian Rhythms in Behaviour and Clock Gene Expression of Drosophila melanogaster

2020 ◽  
Vol 2 (4) ◽  
pp. 434-441
Author(s):  
Nina Li ◽  
Ralf Stanewsky ◽  
Tessa Popay ◽  
Guy Warman ◽  
James Cheeseman
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Circadian Clock ◽  
General Anaesthesia ◽  
Clock Gene ◽  
Night Time ◽  
Clock Gene Expression ◽  
Subjective Night ◽  
Circadian Time ◽  
Concentration Constants

General anaesthesia (GA) is implicated as a cause of postoperative sleep disruption and fatigue with part of the disturbance being attributed to a shift of the circadian clock. In this study, Drosophila melanogaster was used as a model to determine how Isoflurane affects the circadian clock at the behavioural and molecular levels. We measured the response of the clock at both of these levels caused by different durations and different concentrations of Isoflurane at circadian time 4 (CT4). Once characterized, we held the duration and concentration constants (at 2% in air for 6 h) and calculated the phase responses over the entire circadian cycle in both activity and period expression. Phase advances in behaviour were observed during the subjective day, whereas phase delays were associated with subjective night time GA interventions. The corresponding pattern of gene expression preceded the behavioural pattern by approximately four hours. We discuss the implications of this effect for clinical and research practice.

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.

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