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Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-01790-z
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dc.titleDevelopmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1
dc.contributor.authorFujita, K
dc.contributor.authorMao, Y
dc.contributor.authorUchida, S
dc.contributor.authorChen, X
dc.contributor.authorShiwaku, H
dc.contributor.authorTamura, T
dc.contributor.authorIto, H
dc.contributor.authorWatase, K
dc.contributor.authorHomma, H
dc.contributor.authorTagawa, K
dc.contributor.authorSudol, M
dc.contributor.authorOkazawa, H
dc.date.accessioned2020-09-04T02:27:25Z
dc.date.available2020-09-04T02:27:25Z
dc.date.issued2017
dc.identifier.citationFujita, K, Mao, Y, Uchida, S, Chen, X, Shiwaku, H, Tamura, T, Ito, H, Watase, K, Homma, H, Tagawa, K, Sudol, M, Okazawa, H (2017). Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1. Nature Communications 8 (1) : 1864. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-017-01790-z
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/174376
dc.description.abstractYAP and its neuronal isoform YAPdeltaC are implicated in various cellular functions. We found that expression of YAPdeltaC during development, but not adulthood, rescued neurodegeneration phenotypes of mutant ataxin-1 knock-in (Atxn1-KI) mice. YAP/YAPdeltaC interacted with ROR? via the second WW domain and served as co-activators of its transcriptional activity. YAP/YAPdeltaC formed a transcriptional complex with ROR? on cis-elements of target genes and regulated their expression. Both normal and mutant Atxn1 interacted with YAP/YAPdeltaC, but only mutant Atxn1 depleted YAP/YAPdeltaC from the ROR? complex to suppress transcription on short timescales. Over longer periods, mutant Atxn1 also decreased ROR? in vivo. Genetic supplementation of YAPdeltaC restored the ROR? and YAP/YAPdeltaC levels, recovered YAP/YAPdeltaC in the ROR? complex and normalized target gene transcription in Atxn1-KI mice in vivo. Collectively, our data suggest that functional impairment of YAP/YAPdeltaC by mutant Atxn1 during development determines the adult pathology of SCA1 by suppressing ROR?-mediated transcription. © 2017 The Author(s).
dc.publisherNature Publishing Group
dc.sourceUnpaywall 20200831
dc.subjectataxin 1
dc.subjectretinoid related orphan receptor alpha
dc.subjecttranscription factor
dc.subjecttranscription factor YAPdeltaC
dc.subjectunclassified drug
dc.subjectataxin 1
dc.subjectAtxn1 protein, mouse
dc.subjectisoprotein
dc.subjectphosphoprotein
dc.subjectretinoid related orphan receptor alpha
dc.subjectRora protein, mouse
dc.subjectsignal transducing adaptor protein
dc.subjectYap protein, mouse
dc.subjectadult
dc.subjectcells and cell components
dc.subjectdevelopmental biology
dc.subjectgene expression
dc.subjectmutation
dc.subjectnumerical model
dc.subjectpathology
dc.subjectadulthood
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectfunctional disease
dc.subjectgenetic transcription
dc.subjectin vivo study
dc.subjectmale
dc.subjectmouse
dc.subjectnonhuman
dc.subjectprotein domain
dc.subjectprotein expression
dc.subjectprotein protein interaction
dc.subjectspinocerebellar degeneration
dc.subjectsupplementation
dc.subjectanimal
dc.subjectcerebellum
dc.subjectcytology
dc.subjectdisease model
dc.subjectgene expression regulation
dc.subjectgene knock-in
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectnerve cell
dc.subjectpathophysiology
dc.subjectphenotype
dc.subjectrotarod test
dc.subjectspinocerebellar degeneration
dc.subjectMus
dc.subjectAdaptor Proteins, Signal Transducing
dc.subjectAnimals
dc.subjectAtaxin-1
dc.subjectCerebellum
dc.subjectDisease Models, Animal
dc.subjectGene Expression Regulation, Developmental
dc.subjectGene Knock-In Techniques
dc.subjectMale
dc.subjectMice
dc.subjectNeurons
dc.subjectNuclear Receptor Subfamily 1, Group F, Member 1
dc.subjectPhenotype
dc.subjectPhosphoproteins
dc.subjectProtein Isoforms
dc.subjectRotarod Performance Test
dc.subjectSpinocerebellar Ataxias
dc.typeArticle
dc.contributor.departmentPHYSIOLOGY
dc.description.doi10.1038/s41467-017-01790-z
dc.description.sourcetitleNature Communications
dc.description.volume8
dc.description.issue1
dc.description.page1864
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