On the nature of the circadian clock in mammals

1993 ◽  
Vol 264 (5) ◽  
pp. R821-R832 ◽  
Author(s):  
J. D. Miller
Keyword(s):  
Cell Culture ◽  
Functional Analysis ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Response Curve ◽  
Essential Role ◽  
Phase Response Curve ◽  
Coupling Model ◽  
Clock Mechanism

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and non-neuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.

Development and Entrainment of the Fetal Clock in the Suprachiasmatic Nuclei: The Role of Glucocorticoids

2019 ◽  
Vol 34 (3) ◽  
pp. 307-322 ◽  
Author(s):  
Vendula Čečmanová ◽  
Pavel Houdek ◽  
Karolína Šuchmanová ◽  
Martin Sládek ◽  
Alena Sumová
Keyword(s):  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Placental Barrier ◽  
Suprachiasmatic Nuclei ◽  
Pregnant Rats ◽  
Peripheral Tissues ◽  
Pass Through

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2 Luc mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels.

Involvement of protein synthesis in circadian clock of Aplysia eye

1986 ◽  
Vol 250 (1) ◽  
pp. R5-R17
Author(s):  
D. P. Lotshaw ◽  
J. W. Jacklet
Keyword(s):  
Protein Synthesis ◽  
Circadian Clock ◽  
Response Curve ◽  
Phase Response Curve ◽  
Phase Shifting ◽  
Protein Synthesis Inhibition ◽  
Protein Synthesis Inhibitors ◽  
Synthesis Inhibition ◽  
Subjective Night ◽  
Induce Phase

The effects of the protein synthesis inhibitors anisomycin and puromycin were measured on protein synthesis and phase shifting of the circadian rhythm in the isolated Aplysia eye. Anisomycin pulses induce phase delays proportional in magnitude to the duration and percentage of protein synthesis inhibition. The phase-response curve to anisomycin pulses consisted of delays induced throughout the subjective night. Delays were maximal between circadian times (CT) 18 and CT 2; pulses initiated between CT 2 and CT 12 did not phase shift. Puromycin induced phase delays and advances. Delays were proportional to the duration and percentage of protein synthesis inhibition, occurring with increasing magnitude throughout the subjective night (CT 12-2). Peptidyl-puromycin formation may contribute to the magnitude of the delay. Advances, occurring between CT 2 and CT 8, required a greater drug concentration and pulse duration than delays and appeared to result from an effect other than protein synthesis inhibition. Our results support the hypothesis of a phase-dependent requirement for protein synthesis during the subjective night in this circadian clock.

scholarly journals PERIOD phosphoclusters control temperature compensation of the Drosophila circadian clock

2021 ◽  
Author(s):  
Patrick Emery ◽  
Radhika Joshi ◽  
Yao Cai ◽  
Yomgliang Xia ◽  
Joanna Chiu
Keyword(s):  
Cell Culture ◽  
Circadian Clock ◽  
Temperature Compensation ◽  
Thermal Compensation ◽  
Functional Heterogeneity ◽  
Temperature Dependent ◽  
Critical Feature ◽  
Control Temperature ◽  
Functional Homolog

Temperature compensation is a critical feature of circadian rhythms, but how it is achieved remains elusive. Here, we uncovered the important role played by the Drosophila PERIOD (PER) phosphodegron in temperature compensation. Using CRISPR-Cas9, we introduced a series of mutations that altered three Serines (S44, 45 and 47) belonging to the PER phosphodegron, the functional homolog of mammalian PER2’s S487 phosphodegron, which impacts temperature compensation. While all three Serine to Alanine substitutions lengthened period at all temperatures tested, temperature compensation was differentially affected. S44A and S45A substitutions caused decreased temperature compensation, while S47A resulted in overcompensation. These results thus reveal unexpected functional heterogeneity of phosphodegron residues in thermal compensation. Furthermore, mutations impairing phosphorylation of the per^s phosphocluster decreased thermal compensation, consistent with its inhibitory role on S47 phosphorylation. Interestingly,the S47A substitution caused increased accumulation of hyper-phosphorylated PER at warmer temperatures. This finding was corroborated by cell culture assays in which S47A caused excessive temperature compensation of phosphorylation-dependent PER degradation. Thus, we show a novel role of the PER phosphodegron in temperature compensation through temperature-dependent modulation of the abundance of hyper-phosphorylated PER. Our work also reveals interesting mechanistic convergences and differences between mammalian and Drosophila temperature compensation of the circadian clock.

scholarly journals Essential role of spi-1–like (spi-1l) in zebrafish myeloid cell differentiation

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 2038-2046 ◽  
Author(s):  
Alex Bukrinsky ◽  
Kevin J. P. Griffin ◽  
Yan Zhao ◽  
Shuo Lin ◽  
Utpal Banerjee
Keyword(s):  
Functional Analysis ◽  
Transcription Factor ◽  
Cell Differentiation ◽  
Essential Role ◽  
Critical Role ◽  
Myeloid Cell ◽  
Myeloid Differentiation ◽  
Adult Kidney ◽  
Necessary And Sufficient

The ETS protein Spi-1/Pu.1 plays a pivotal and widespread role throughout hematopoiesis in many species. This study describes the identification, characterization, and functional analysis of a new zebrafish spi transcription factor spi-1–like (spi-1l) that is expressed in primitive myeloid cells, erythro-myelo progenitor cells, and in the adult kidney. Spi-1l functions genetically downstream of etsrp, scl, and spi-1/pu.1 in myeloid differentiation. Spi-1l is coexpressed in a subset of spi-1/pu.1 cells and its function is necessary and sufficient for macrophage and granulocyte differentiation. These results establish a critical role for spi-1l in zebrafish myeloid cell differentiation.

scholarly journals RNAi of the circadian clock gene period disrupts the circadian rhythm but not the circatidal rhythm in the mangrove cricket

2012 ◽  
Vol 8 (4) ◽  
pp. 488-491 ◽  
Author(s):  
Hiroki Takekata ◽  
Yu Matsuura ◽  
Shin G. Goto ◽  
Aya Satoh ◽  
Hideharu Numata
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Molecular Basis ◽  
Clock Gene ◽  
Circadian Clock Gene ◽  
Double Stranded Rna ◽  
Activity Intensity ◽  
Significant Difference ◽  
Clock Mechanism

The clock mechanism for circatidal rhythm has long been controversial, and its molecular basis is completely unknown. The mangrove cricket, Apteronemobius asahinai , shows two rhythms simultaneously in its locomotor activity: a circatidal rhythm producing active and inactive phases as well as a circadian rhythm modifying the activity intensity of circatidal active phases. The role of the clock gene period ( per ), one of the key components of the circadian clock in insects, was investigated in the circadian and circatidal rhythms of A. asahinai using RNAi. After injection of double-stranded RNA of per , most crickets did not show the circadian modulation of activity but the circatidal rhythm persisted without a significant difference in the period from controls. Thus, per is functionally involved in the circadian rhythm but plays no role, or a less important role, in the circatidal rhythm. We conclude that the circatidal rhythm in A. asahinai is controlled by a circatidal clock whose molecular mechanism is different from that of the circadian clock.

scholarly journals The day/night difference in the circadian clock’s response to acute lipopolysaccharide and the rhythmic Stat3 expression in the rat suprachiasmatic nucleus

2018 ◽  
Author(s):  
Simona Moravcová ◽  
Dominika Pačesová ◽  
Barbora Melkes ◽  
Hana Kyclerová ◽  
Veronika Spišská ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Activity Patterns ◽  
Night Time ◽  
Male Wistar Rats ◽  
And Function ◽  
External Signals

AbstractThe circadian clock in the suprachiasmatic nucleus (SCN) regulates daily rhythms in physiology and behaviour and is an important part of the mammalian homeostatic system. Previously, we have shown that systemic inflammatory stimulation with lipopolysaccharide (LPS) induced the daytime-dependent phosphorylation of STAT3 in the SCN. Here, we demonstrate the LPS-induced Stat3 mRNA expression in the SCN and show also the circadian rhythm in Stat3 expression in the SCN, with high levels during the day. Moreover, we examined the effects of LPS (1mg/kg), applied either during the day or the night, on the rhythm in locomotor activity of male Wistar rats. We observed that recovery of normal locomotor activity patterns took longer when the animals were injected during the night. The clock genes Per1, Per2 and Nr1d1, and phosphorylation of kinases ERK1/2 and GSK3β are sensitive to external cues and function as the molecular entry for external signals into the circadian clockwork. We also studied the immediate changes in these clock genes expressions and the phosphorylation of ERK1/2 and GSK3β in the suprachiasmatic nucleus in response to daytime or night-time inflammatory stimulation. We revealed mild and transient changes with respect to the controls. Our data stress the role of STAT3 in the circadian clock response to the LPS and provide further evidence of the interaction between the circadian clock and immune system.

scholarly journals Essential Role of the NV Protein of Novirhabdovirus for Pathogenicity in Rainbow Trout

2004 ◽  
Vol 78 (8) ◽  
pp. 4098-4107 ◽  
Author(s):  
Maria-Isabel Thoulouze ◽  
Edwige Bouguyon ◽  
Catherine Carpentier ◽  
Michel Brémont
Keyword(s):  
Cell Culture ◽  
Essential Role ◽  
Reverse Genetics ◽  
Fluorescent Protein ◽  
Normal Growth ◽  
Viral Hemorrhagic Septicemia Virus ◽  
Fish Cell ◽  
Reading Frame ◽  
Juvenile Trout

ABSTRACT Novirhabdovirus, infectious hematopoietic necrosis virus (IHNV), and viral hemorrhagic septicemia virus (VHSV) are fish rhabdoviruses that, in comparison to the other rhabdoviruses, contain an additional gene coding for a small nonvirion (NV) protein of unassigned function. A recombinant IHNV with the NV gene deleted but expressing the green fluorescent protein (rIHNV-ΔNV) has previously been shown to be efficiently recovered by reverse genetics (S. Biacchesi et al., J. Virol. 74:11247-11253, 2000). However, preliminary experiments suggested that the growth in cell culture of rIHNV-ΔNV was affected by the NV deletion. In the present study, we show that the growth in cell culture of rIHNV-ΔNV is indeed severely impaired but that a normal growth of rIHNV-ΔNV can be restored when NV is provided in trans by using fish cell clones constitutively expressing the NV protein. These results indicate that NV is a protein that has a crucial biological role for optimal replication of IHNV in cell culture. Although IHNV and VHSV NV proteins do not share any significant identity, we show here that both NV proteins play a similar role since a recombinant IHNV virus, rIHNV-NVVHSV, in which the IHNV NV open reading frame has been replaced by that of VHSV, was shown to replicate as well as the wild-type (wt) IHNV into fish cells. Finally, data provided by experimental fish infections with the various recombinant viruses strongly suggest an essential role of the NV protein for the pathogenicity of IHNV. Furthermore, we show that juvenile trout immunized with NV-knockout IHNV were protected against challenge with wt IHNV. That opens a new perspective for the development of IHNV attenuated live vaccines.

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