title: Diversification of the molecular clockwork for tissue-specific function: insight from a novel Drosophila Clock mutant homologous to a mouse Clock allele.
abstract: The circadian clock system enables organisms to anticipate the rhythmic environmental changes and to manifest behavior and physiology at advantageous times of the day. Transcriptional/translational feedback loop (TTFL) is the basic feature of the eukaryotic circadian clock and is based on the rhythmic association of circadian transcriptional activator and repressor. In Drosophila, repression of dCLOCK/CYCLE (dCLK/CYC) mediated transcription by PERIOD (PER) is critical for inducing circadian rhythms of gene expression. Pacemaker neurons in the brain control specific circadian behaviors upon environmental timing cues such as light and temperature cycle. We show here that amino acids 657-707 of dCLK are important for the transcriptional activation and the association with PER both in vitro and in vivo. Flies expressing dCLK lacking AA657-707 in Clkout genetic background, homologous to the mouse Clock allele where exon 19 region is deleted, display pacemaker-neuron-dependent perturbation of the molecular clockwork. The molecular rhythms in light-cycle-sensitive pacemaker neurons such as ventral lateral neurons (LNvs) were significantly disrupted, but those in temperature-cycle-sensitive pacemaker neurons such as dorsal neurons (DNs) were robust. Our results suggest that the dCLK-controlled TTFL diversify in a pacemaker-neuron-dependent manner which may contribute to specific functions such as different sensitivities to entraining cues. [BMB Reports 2016; 49(11): 587-589].
authors.affiliation: Department of Brain Science and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Cho
authors.affiliation: Chronic Inflammatory Disease Research Center and BK21 Plus program, Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 16499, Korea.
authors.forename: Euna
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, KAIST; Cellex Life Sciences Inc.; Cancer Metastasis Control Center, KAIST Institute for the Biocentury, KAIST, Daejeon 34141, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
mesh_terms: D000483:Alleles; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D025461:Feedback, Physiological; D051379:Mice; D009474:Neurons / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D056950:Period Circadian Proteins; D056926:CLOCK Proteins