| First Author | Fujita K | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1864 |
| PubMed ID | 29192206 | Mgi Jnum | J:255878 |
| Mgi Id | MGI:6106310 | Doi | 10.1038/s41467-017-01790-z |
| Citation | Fujita K, et al. (2017) Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1. Nat Commun 8(1):1864 |
| abstractText | 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 RORalpha via the second WW domain and served as co-activators of its transcriptional activity. YAP/YAPdeltaC formed a transcriptional complex with RORalpha 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 RORalpha complex to suppress transcription on short timescales. Over longer periods, mutant Atxn1 also decreased RORalpha in vivo. Genetic supplementation of YAPdeltaC restored the RORalpha and YAP/YAPdeltaC levels, recovered YAP/YAPdeltaC in the RORalpha 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 RORalpha-mediated transcription. |
