DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Choe, Joonho | - |
dc.contributor.advisor | 최준호 | - |
dc.contributor.author | Kweon, Sin Ho | - |
dc.date.accessioned | 2019-08-22T02:44:28Z | - |
dc.date.available | 2019-08-22T02:44:28Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=827901&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/264825 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명과학과, 2018.8,[vii, 107 p. :] | - |
dc.description.abstract | Post-translational control is a crucial mechanism for circadian timekeeping. Evolutionarily conserved kinases and phosphatases have been implicated in circadian phosphorylation and degradation of clock-relevant proteins, which sustain high-amplitude rhythms with 24 hr periodicity in animal behaviors and physiology. Here, we report a novel clock function of the heterodimeric $Ca^{2+}$/calmodulin-dependent phosphatase calcineurin and its regulator sarah (sra) in Drosophila. Genomic deletion of the sra locus dampened circadian locomotor activity rhythms in free-running constant dark after entrainment in light–dark cycles. Poor rhythms in sra mutant behaviors were accompanied by lower expression of two oscillating clock proteins, PERIOD(PER) and TIMELESS(TIM), at the post-transcriptional level. RNA interference–mediated sra depletion in circadian pacemaker neurons was sufficient to phenocopy loss-of-function mutation in sra. On the other hand, a constitutively active form of the catalytic calcineurin subunit, Pp2B-$14D^{ACT}$, shortened circadian periodicity in locomotor behaviors and phase-advanced PER and TIM rhythms when overexpressed in clock neurons. Heterozygous sra deletion induced behavioral arrhythmicity in Pp2B-$14D^{ACT}$ flies, whereas sra overexpression rescued short periods in these animals. Finally, pharmacological inhibition of calcineurin in either wild-type flies or clock-less S2 cells decreased the levels of PER and TIM, likely by facilitating their proteasomal degradation. Taken together, these data suggest that sra negatively regulates calcineurin by cell-autonomously titrating calcineurin-dependent stabilization of PER and TIM proteins, thereby sustaining high-amplitude behavioral rhythms in Drosophila. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Drosophila▼acircadian rhythms▼acalcineurin▼asarah▼apost-translational regulation | - |
dc.subject | 초파리▼a생체리듬▼a번역 후 단백질 조절 | - |
dc.title | Characterization of the circadian regulating gene Sarah in drosophila melanogaster | - |
dc.title.alternative | 초파리 생체리듬 조절 유전자 Sarah의 기능 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :생명과학과, | - |
dc.contributor.alternativeauthor | 권신호 | - |
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