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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 |
| Appears in Collections: | Elements Staff Publications |
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