| Budget Amount *help |
¥207,090,000 (Direct Cost: ¥159,300,000、Indirect Cost: ¥47,790,000)
Fiscal Year 2017: ¥28,990,000 (Direct Cost: ¥22,300,000、Indirect Cost: ¥6,690,000)
Fiscal Year 2016: ¥38,740,000 (Direct Cost: ¥29,800,000、Indirect Cost: ¥8,940,000)
Fiscal Year 2015: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
Fiscal Year 2014: ¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000)
Fiscal Year 2013: ¥54,730,000 (Direct Cost: ¥42,100,000、Indirect Cost: ¥12,630,000)
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| Outline of Final Research Achievements |
The aim of this study is to understand the molecular mechanisms driving the temperature-compensated mammalian circadian clock through reconstitution. CKIδ determines the period of mammalian circadian clocks and its kinase activity is almost unchanged under physiological temperature range. We found that the temperature compensation is achieved through 1) decreased kinase-substrate affinity and 2) elevated affinity between the kinase and a phosphorylated product. We further identified the responsible domain of CKIδ for the temperature-dependent product binding. The domain can confer temperature compensation on the otherwise temperature-sensitive kinase. Behavioral circadian period as well as temperature sensitivity of circadian period of SCN was significantly altered in the genetically modified mice having the mutant CKIδ. In summary, we uncovered the molecular mechanism underlying the temperature-compensation of CKIδaction in vitro, and partly its physiological significance in vivo.
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