Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-017-01790-z
Title: Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1
Authors: Fujita, K
Mao, Y
Uchida, S
Chen, X
Shiwaku, H
Tamura, T
Ito, H
Watase, K
Homma, H
Tagawa, K
Sudol, M 
Okazawa, H
Keywords: ataxin 1
retinoid related orphan receptor alpha
transcription factor
transcription factor YAPdeltaC
unclassified drug
ataxin 1
Atxn1 protein, mouse
isoprotein
phosphoprotein
retinoid related orphan receptor alpha
Rora protein, mouse
signal transducing adaptor protein
Yap protein, mouse
adult
cells and cell components
developmental biology
gene expression
mutation
numerical model
pathology
adulthood
animal cell
animal experiment
animal model
animal tissue
Article
controlled study
functional disease
genetic transcription
in vivo study
male
mouse
nonhuman
protein domain
protein expression
protein protein interaction
spinocerebellar degeneration
supplementation
animal
cerebellum
cytology
disease model
gene expression regulation
gene knock-in
genetics
metabolism
nerve cell
pathophysiology
phenotype
rotarod test
spinocerebellar degeneration
Mus
Adaptor Proteins, Signal Transducing
Animals
Ataxin-1
Cerebellum
Disease Models, Animal
Gene Expression Regulation, Developmental
Gene Knock-In Techniques
Male
Mice
Neurons
Nuclear Receptor Subfamily 1, Group F, Member 1
Phenotype
Phosphoproteins
Protein Isoforms
Rotarod Performance Test
Spinocerebellar Ataxias
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Fujita, 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
Abstract: YAP 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).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/174376
ISSN: 2041-1723
DOI: 10.1038/s41467-017-01790-z
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