Circadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism in Neurospora crassa

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dc.contributor.authorBaek, Mokryun
dc.contributor.authorVirgilio, Stela [UNESP]
dc.contributor.authorLamb, Teresa M.
dc.contributor.authorIbarra, Oneida
dc.contributor.authorAndrade, Juvana Moreira [UNESP]
dc.contributor.authorGoncalves, Rodrigo Duarte [UNESP]
dc.contributor.authorDovzhenok, Andrey
dc.contributor.authorLim, Sookkyung
dc.contributor.authorBell-Pedersen, Deborah
dc.contributor.authorBertolini, Maria Celia [UNESP]
dc.contributor.authorHong, Christian I.
dc.contributor.institutionUniv Cincinnati
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionTexas A&M Univ
dc.date.accessioned2019-10-04T12:37:58Z
dc.date.available2019-10-04T12:37:58Z
dc.date.issued2019-05-21
dc.description.abstractCircadian clocks generate rhythms in cellular functions, including metabolism, to align biological processes with the 24-hour environment. Disruption of this alignment by shift work alters glucose homeostasis. Glucose homeostasis depends on signaling and allosteric control; however, the molecular mechanisms linking the clock to glucose homeostasis remain largely unknown. We investigated the molecular links between the clock and glycogen metabolism, a conserved glucose homeostatic process, in Neurospora crassa. We find that glycogen synthase (gsn) mRNA, glycogen phosphorylase (gpn) mRNA, and glycogen levels, accumulate with a daily rhythm controlled by the circadian clock. Because the synthase and phosphorylase are critical to homeostasis, their roles in generating glycogen rhythms were investigated. We demonstrate that while gsn was necessary for glycogen production, constitutive gsn expression resulted in high and arrhythmic glycogen levels, and deletion of gpn abolished gsn mRNA rhythms and rhythmic glycogen accumulation. Furthermore, we show that gsn promoter activity is rhythmic and is directly controlled by core clock component white collar complex (WCC). We also discovered that WCC-regulated transcription factors, VOS-1 and CSP-1, modulate the phase and amplitude of rhythmic gsn mRNA, and these changes are similarly reflected in glycogen oscillations. Together, these data indicate the importance of clock-regulated gsn transcription over signaling or allosteric control of glycogen rhythms, a mechanism that is potentially conserved in mammals and critical to metabolic homeostasis.en
dc.description.affiliationUniv Cincinnati, Dept Pharmacol & Syst Physiol, Cincinnati, OH 45267 USA
dc.description.affiliationUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14800060 Araraquara, SP, Brazil
dc.description.affiliationTexas A&M Univ, Dept Biol, College Stn, TX 77843 USA
dc.description.affiliationUniv Cincinnati, Dept Math Sci, Cincinnati, OH 45221 USA
dc.description.affiliationUniv Cincinnati, Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Dev Biol, Cincinnati, OH 45229 USA
dc.description.affiliationUnespUniv Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, BR-14800060 Araraquara, SP, Brazil
dc.description.sponsorshipNeurospora Functional Genomics Grant
dc.description.sponsorshipNIH
dc.description.sponsorshipDepartment of Interior Grant
dc.description.sponsorshipCollege of Medicine Dean's support fund from University of Cincinnati
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdNeurospora Functional Genomics Grant: P01GM68087
dc.description.sponsorshipIdNIH: GM126966
dc.description.sponsorshipIdNIH: GM106426
dc.description.sponsorshipIdNIH: GM113673
dc.description.sponsorshipIdDepartment of Interior Grant: D12AP00005
dc.description.sponsorshipIdFAPESP: 2013/14513-0
dc.description.sponsorshipIdFAPESP: 2013/24705-3
dc.format.extent10435-10440
dc.identifierhttp://dx.doi.org/10.1073/pnas.1815360116
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America. Washington: Natl Acad Sciences, v. 116, n. 21, p. 10435-10440, 2019.
dc.identifier.doi10.1073/pnas.1815360116
dc.identifier.issn0027-8424
dc.identifier.lattes8817669953838863
dc.identifier.urihttp://hdl.handle.net/11449/185726
dc.identifier.wosWOS:000468403400044
dc.language.isoeng
dc.publisherNatl Acad Sciences
dc.relation.ispartofProceedings Of The National Academy Of Sciences Of The United States Of America
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectcircadian rhythms
dc.subjectNeurospora crassa
dc.subjectglycogen metabolism
dc.subjectglycogen synthase
dc.subjectglycogen phosphorylase
dc.titleCircadian clock regulation of the glycogen synthase (gsn) gene by WCC is critical for rhythmic glycogen metabolism in Neurospora crassaen
dc.typeArtigo
dcterms.rightsHolderNatl Acad Sciences
unesp.author.lattes8817669953838863
unesp.author.orcid0000-0002-1639-8215[9]

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