TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/62203 |
Resumo: | Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically and physically interacts with CycA to promote sleep. Furthermore, decreased levels of Cyclin-dependent kinase 1 (Cdk1), a kinase partner of CycA, rescue the short-sleeping phenotype of tara and CycA mutants, while increased Cdk1 activity mimics the tara and CycA phenotypes, suggesting that Cdk1 mediates the role of TARA and CycA in sleep regulation. Finally, we describe a novel wake-promoting role for a cluster of ∼14 CycA-expressing neurons in the pars lateralis (PL), previously proposed to be analogous to the mammalian hypothalamus. We propose that TARANIS controls sleep amount by regulating CycA protein levels and inhibiting Cdk1 activity in a novel arousal center. |
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TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in DrosophilaAnimalsArousalBlotting, WesternCDC2 Protein KinaseCell Cycle ProteinsCyclin ADrosophilaDrosophila ProteinsGene Knockdown TechniquesNeuronsPars ReticulataRNA InterferenceSleepCiências Médicas::Medicina BásicaScience & TechnologySleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically and physically interacts with CycA to promote sleep. Furthermore, decreased levels of Cyclin-dependent kinase 1 (Cdk1), a kinase partner of CycA, rescue the short-sleeping phenotype of tara and CycA mutants, while increased Cdk1 activity mimics the tara and CycA phenotypes, suggesting that Cdk1 mediates the role of TARA and CycA in sleep regulation. Finally, we describe a novel wake-promoting role for a cluster of ∼14 CycA-expressing neurons in the pars lateralis (PL), previously proposed to be analogous to the mammalian hypothalamus. We propose that TARANIS controls sleep amount by regulating CycA protein levels and inhibiting Cdk1 activity in a novel arousal center.National Institutes of Health (R01GM088221 to K.K.) and predoctoral fellowships from the Portuguese Foundation for Science and Technology (SFRH/BD/51726/2011 to D.J.S.A. and SFRH/BD/52321/2013 to D.R.M.). Sequencing was performed at the Kimmel Cancer Center Nucleic Acid Facility, which is supported by a grant from the NIH (P30CA56036)ElsevierUniversidade do MinhoAfonso, Dinis J. S.Liu, DieMachado, Daniel R.Pan, HuihuiJepson, James E. C.Rogulja, DraganaKoh, Kyunghee2015-06-292015-06-29T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/62203engAfonso, D. J., Liu, D., Machado, D. R., Pan, H., Jepson, J. E., Rogulja, D., & Koh, K. (2015). TARANIS functions with cyclin A and Cdk1 in a novel arousal center to control sleep in Drosophila. Current Biology, 25(13), 1717-1726.0960-98221879-044510.1016/j.cub.2015.05.03726096977https://www.sciencedirect.com/science/article/pii/S0960982215006119info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:53:55Zoai:repositorium.sdum.uminho.pt:1822/62203Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:53:25.088954Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
title |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
spellingShingle |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila Afonso, Dinis J. S. Animals Arousal Blotting, Western CDC2 Protein Kinase Cell Cycle Proteins Cyclin A Drosophila Drosophila Proteins Gene Knockdown Techniques Neurons Pars Reticulata RNA Interference Sleep Ciências Médicas::Medicina Básica Science & Technology |
title_short |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
title_full |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
title_fullStr |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
title_full_unstemmed |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
title_sort |
TARANIS Functions with Cyclin A and Cdk1 in a Novel Arousal Center to Control Sleep in Drosophila |
author |
Afonso, Dinis J. S. |
author_facet |
Afonso, Dinis J. S. Liu, Die Machado, Daniel R. Pan, Huihui Jepson, James E. C. Rogulja, Dragana Koh, Kyunghee |
author_role |
author |
author2 |
Liu, Die Machado, Daniel R. Pan, Huihui Jepson, James E. C. Rogulja, Dragana Koh, Kyunghee |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Afonso, Dinis J. S. Liu, Die Machado, Daniel R. Pan, Huihui Jepson, James E. C. Rogulja, Dragana Koh, Kyunghee |
dc.subject.por.fl_str_mv |
Animals Arousal Blotting, Western CDC2 Protein Kinase Cell Cycle Proteins Cyclin A Drosophila Drosophila Proteins Gene Knockdown Techniques Neurons Pars Reticulata RNA Interference Sleep Ciências Médicas::Medicina Básica Science & Technology |
topic |
Animals Arousal Blotting, Western CDC2 Protein Kinase Cell Cycle Proteins Cyclin A Drosophila Drosophila Proteins Gene Knockdown Techniques Neurons Pars Reticulata RNA Interference Sleep Ciências Médicas::Medicina Básica Science & Technology |
description |
Sleep is an essential and conserved behavior whose regulation at the molecular and anatomical level remains to be elucidated. Here, we identify TARANIS (TARA), a Drosophila homolog of the Trip-Br (SERTAD) family of transcriptional coregulators, as a molecule that is required for normal sleep patterns. Through a forward-genetic screen, we isolated tara as a novel sleep gene associated with a marked reduction in sleep amount. Targeted knockdown of tara suggests that it functions in cholinergic neurons to promote sleep. tara encodes a conserved cell-cycle protein that contains a Cyclin A (CycA)-binding homology domain. TARA regulates CycA protein levels and genetically and physically interacts with CycA to promote sleep. Furthermore, decreased levels of Cyclin-dependent kinase 1 (Cdk1), a kinase partner of CycA, rescue the short-sleeping phenotype of tara and CycA mutants, while increased Cdk1 activity mimics the tara and CycA phenotypes, suggesting that Cdk1 mediates the role of TARA and CycA in sleep regulation. Finally, we describe a novel wake-promoting role for a cluster of ∼14 CycA-expressing neurons in the pars lateralis (PL), previously proposed to be analogous to the mammalian hypothalamus. We propose that TARANIS controls sleep amount by regulating CycA protein levels and inhibiting Cdk1 activity in a novel arousal center. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-06-29 2015-06-29T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/62203 |
url |
http://hdl.handle.net/1822/62203 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Afonso, D. J., Liu, D., Machado, D. R., Pan, H., Jepson, J. E., Rogulja, D., & Koh, K. (2015). TARANIS functions with cyclin A and Cdk1 in a novel arousal center to control sleep in Drosophila. Current Biology, 25(13), 1717-1726. 0960-9822 1879-0445 10.1016/j.cub.2015.05.037 26096977 https://www.sciencedirect.com/science/article/pii/S0960982215006119 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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