scholarly journals Cross-scale Analysis of Temperature Compensation in the Cyanobacterial Circadian Clock System

2021 ◽  
Author(s):  
Yoshihiko Furuike ◽  
Dongyan Ouyang ◽  
Taiki Tominaga ◽  
Tatsuhito Matsuo ◽  
Atsushi Mukaiyama ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Temperature Compensation ◽  
Thermal Fluctuation ◽  
System Level ◽  
Dependent Manner ◽  
Clock System ◽  
Terminal Domain ◽  
Internal Motions ◽  
Clock Proteins ◽  
Quasielastic Neutron

Clock proteins maintain constant enzymatic activity regardless of temperature, even though thermal fluctuation is accelerated as temperature increases. We investigated temperature influences on the dynamics of KaiC, a temperature-compensated ATPase in the cyanobacterial circadian clock system, using quasielastic neutron scattering. The frequency of picosecond to sub-nanosecond incoherent local motions in KaiC was accelerated very slightly in a temperature-dependent manner. Our mutation studies revealed that internal motions of KaiC include several contributions of opposing temperature sensitivities. To take advantage of this balancing effect, the motional frequency of local dynamics in KaiC needs to exceed ~0.3 ps-1. Some of the mutation sites may be in a pathway through which the motional frequency in the C-terminal domain of KaiC is fed back to the active site of ATPase in its N-terminal domain. The temperature-compensating ability at the dynamics level is likely crucial for circadian clock systems, into which the clock proteins are incorporated, to achieve reaction- or even system-level temperature compensation of the oscillation frequency.

scholarly journals Direct Association between Mouse PERIOD and CKIε Is Critical for a Functioning Circadian Clock

2004 ◽  
Vol 24 (2) ◽  
pp. 584-594 ◽  
Author(s):  
Choogon Lee ◽  
David R. Weaver ◽  
Steven M. Reppert
Keyword(s):  
Circadian Clock ◽  
Double Mutant ◽  
Mutant Mice ◽  
Chimeric Proteins ◽  
Posttranslational Regulation ◽  
Dependent Manner ◽  
Clock Proteins ◽  
Deficient Mice

ABSTRACT The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable. Here we examine the posttranslational regulation of mPER3 in vivo in mouse liver and compare it to the other mPER proteins to define the salient features required for clock function. Like mPER1 and mPER2, mPER3 is phosphorylated, changes cellular location, and interacts with other clock proteins in a time-dependent manner. Consistent with behavioral data from mPer2/3 and mPer1/3 double-mutant mice, either mPER1 or mPER2 alone can sustain rhythmic posttranslational events. However, mPER3 is unable to sustain molecular rhythmicity in mPer1/2 double-mutant mice. Indeed, mPER3 is always cytoplasmic and is not phosphorylated in the livers of mPer1-deficient mice, suggesting that mPER3 is regulated by mPER1 at a posttranslational level. In vitro studies with chimeric proteins suggest that the inability of mPER3 to support circadian clock function results in part from lack of direct and stable interaction with casein kinase Iε (CKIε). We thus propose that the CKIε-binding domain is critical not only for mPER phosphorylation but also for a functioning circadian clock.

scholarly journals FRQ-CK1 Interaction Underlies Temperature Compensation of the Neurospora Circadian Clock

mBio ◽  
2021 ◽  
Author(s):  
Yue Hu ◽  
Xiaolan Liu ◽  
Qiaojia Lu ◽  
Yulin Yang ◽  
Qun He ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Temperature Compensation ◽  
Period Length ◽  
Clock Proteins ◽  
Constant Period

Temperature compensation allows clocks to adapt to all seasons by having a relatively constant period length at different physiological temperatures, but the mechanism of temperature compensation is unclear. Stability of clock proteins was previously proposed to be a major factor that regulated temperature compensation.

scholarly journals Clock proteins and training modify exercise capacity in a daytime-dependent manner

2021 ◽  
Vol 118 (35) ◽  
pp. e2101115118
Author(s):  
Yaarit Adamovich ◽  
Vaishnavi Dandavate ◽  
Saar Ezagouri ◽  
Gal Manella ◽  
Ziv Zwighaft ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Feeding Behavior ◽  
Exercise Capacity ◽  
Active Phase ◽  
Liver Glycogen ◽  
Dependent Manner ◽  
Muscle Lipid ◽  
Clock Proteins ◽  
Glycogen Stores

Exercise and circadian biology are closely intertwined with physiology and metabolism, yet the functional interaction between circadian clocks and exercise capacity is only partially characterized. Here, we tested different clock mutant mouse models to examine the effect of the circadian clock and clock proteins, namely PERIODs and BMAL1, on exercise capacity. We found that daytime variance in endurance exercise capacity is circadian clock controlled. Unlike wild-type mice, which outperform in the late compared with the early part of their active phase, PERIODs- and BMAL1-null mice do not show daytime variance in exercise capacity. It appears that BMAL1 impairs and PERIODs enhance exercise capacity in a daytime-dependent manner. An analysis of liver and muscle glycogen stores as well as muscle lipid utilization suggested that these daytime effects mostly relate to liver glycogen levels and correspond to the animals’ feeding behavior. Furthermore, given that exercise capacity responds to training, we tested the effect of training at different times of the day and found that training in the late compared with the early part of the active phase improves exercise performance. Overall, our findings suggest that clock proteins shape exercise capacity in a daytime-dependent manner through changes in liver glycogen levels, likely due to their effect on animals’ feeding behavior.

scholarly journals Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth

2019 ◽  
Vol 5 (1) ◽  
pp. eaau9060 ◽  
Author(s):  
Tsuyoshi Oshima ◽  
Yoshimi Niwa ◽  
Keiko Kuwata ◽  
Ashutosh Srivastava ◽  
Tomoko Hyoda ◽  
...  
Keyword(s):  
Cell Growth ◽  
Circadian Clock ◽  
Cancer Cell ◽  
Direct Interaction ◽  
Cancer Cell Growth ◽  
X Ray ◽  
Clock Proteins ◽  
Target Deconvolution ◽  
Phenotypic Screen ◽  
Dependent Inhibition

Compounds targeting the circadian clock have been identified as potential treatments for clock-related diseases, including cancer. Our cell-based phenotypic screen revealed uncharacterized clock-modulating compounds. Through affinity-based target deconvolution, we identified GO289, which strongly lengthened circadian period, as a potent and selective inhibitor of CK2. Phosphoproteomics identified multiple phosphorylation sites inhibited by GO289 on clock proteins, including PER2 S693. Furthermore, GO289 exhibited cell type–dependent inhibition of cancer cell growth that correlated with cellular clock function. The x-ray crystal structure of the CK2α-GO289 complex revealed critical interactions between GO289 and CK2-specific residues and no direct interaction of GO289 with the hinge region that is highly conserved among kinases. The discovery of GO289 provides a direct link between the circadian clock and cancer regulation and reveals unique design principles underlying kinase selectivity.

scholarly journals How is the inner circadian clock controlled by interactive clock proteins?

FEBS Letters ◽  
2015 ◽  
Vol 589 (14) ◽  
pp. 1516-1529 ◽  
Author(s):  
Torsten Merbitz-Zahradnik ◽  
Eva Wolf
Keyword(s):  
Circadian Clock ◽  
Clock Proteins

scholarly journals Epistatic and Synergistic Interactions Between Circadian Clock Mutations in Neurospora crassa

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 537-543
Author(s):  
Louis W Morgan ◽  
Jerry F Feldman
Keyword(s):  
Circadian Clock ◽  
Neurospora Crassa ◽  
Mutant Strain ◽  
Temperature Compensation ◽  
Double Mutant ◽  
Synergistic Interactions ◽  
Long Period ◽  
Double Mutant Strain ◽  
Short Period ◽  
Compensation Mechanisms

Abstract We identified a series of epistatic and synergistic interactions among the circadian clock mutations of Neurospora crassa that indicate possible physical interactions among the various clock components encoded by these genes. The period-6 (prd-6) mutation, a short-period temperature-sensitive clock mutation, is epistatic to both the prd-2 and prd-3 mutations. The prd-2 and prd-3 long-period mutations show a synergistic interaction in that the period length of the double mutant strain is considerably longer than predicted. In addition, the prd-2 prd-3 double mutant strain also exhibits overcompensation to changes in ambient temperature, suggesting a role in the temperature compensation machinery of the clock. The prd-2, prd-3, and prd-6 mutations also show significant interactions with the frq7 long-period mutation. These results suggest that the gene products of prd-2, prd-3, and prd-6 play an important role in both the timing and temperature compensation mechanisms of the circadian clock and may interact with the FRQ protein.

scholarly journals Circadian Clock Proteins in Prokaryotes: Hidden Rhythms?

2010 ◽  
Vol 1 ◽  
Author(s):  
Maria Loza-Correa ◽  
Laura Gomez-Valero ◽  
Carmen Buchrieser
Keyword(s):  
Circadian Clock ◽  
Clock Proteins ◽  
Circadian Clock Proteins
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