DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kweon, Sin Ho | ko |
dc.contributor.author | Lee, Jongbin | ko |
dc.contributor.author | Lim, Chunghun | ko |
dc.contributor.author | Choe, Joonho | ko |
dc.date.accessioned | 2018-08-20T06:48:49Z | - |
dc.date.available | 2018-08-20T06:48:49Z | - |
dc.date.created | 2018-07-25 | - |
dc.date.created | 2018-07-25 | - |
dc.date.created | 2018-07-25 | - |
dc.date.created | 2018-07-25 | - |
dc.date.created | 2018-07-25 | - |
dc.date.created | 2018-07-25 | - |
dc.date.issued | 2018-07 | - |
dc.identifier.citation | GENETICS, v.209, no.3, pp.815 - 828 | - |
dc.identifier.issn | 0016-6731 | - |
dc.identifier.uri | http://hdl.handle.net/10203/244664 | - |
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 the 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 Ca2+/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 | English | - |
dc.publisher | GENETICS SOCIETY AMERICA | - |
dc.title | High-Amplitude Circadian Rhythms in Drosophila Driven by Calcineurin-Mediated Post-translational Control of sarah | - |
dc.type | Article | - |
dc.identifier.wosid | 000437171700014 | - |
dc.identifier.scopusid | 2-s2.0-85049689799 | - |
dc.type.rims | ART | - |
dc.citation.volume | 209 | - |
dc.citation.issue | 3 | - |
dc.citation.beginningpage | 815 | - |
dc.citation.endingpage | 828 | - |
dc.citation.publicationname | GENETICS | - |
dc.identifier.doi | 10.1534/genetics.118.300808 | - |
dc.contributor.localauthor | Lim, Chunghun | - |
dc.contributor.localauthor | Choe, Joonho | - |
dc.contributor.nonIdAuthor | Kweon, Sin Ho | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Drosophila | - |
dc.subject.keywordAuthor | circadian rhythms | - |
dc.subject.keywordAuthor | calcineurin | - |
dc.subject.keywordAuthor | sarah | - |
dc.subject.keywordAuthor | post-translational regulation | - |
dc.subject.keywordPlus | SYNDROME CRITICAL REGION | - |
dc.subject.keywordPlus | CLOCKWORK-ORANGE | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL REPRESSOR | - |
dc.subject.keywordPlus | PACEMAKER NEURONS | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | PERIOD PROTEIN | - |
dc.subject.keywordPlus | DOWN-SYNDROME | - |
dc.subject.keywordPlus | POSTTRANSCRIPTIONAL REGULATION | - |
dc.subject.keywordPlus | STRIATED-MUSCLES | - |
dc.subject.keywordPlus | BINDING PROTEIN | - |
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