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Article: Planar cell polarity gene Fuz triggers apoptosis in neurodegenerative disease models

TitlePlanar cell polarity gene Fuz triggers apoptosis in neurodegenerative disease models
Authors
KeywordsTau
Yin Yang 1
polyglutamine
alpha-synuclein
amyloid beta-peptide
Issue Date2018
Citation
EMBO Reports, 2018, v. 19, n. 9, article no. e45409 How to Cite?
AbstractPlanar cell polarity (PCP) describes a cell–cell communication process through which individual cells coordinate and align within the plane of a tissue. In this study, we show that overexpression of Fuz, a PCP gene, triggers neuronal apoptosis via the dishevelled/Rac1 GTPase/MEKK1/JNK/caspase signalling axis. Consistent with this finding, endogenous Fuz expression is upregulated in models of polyglutamine (polyQ) diseases and in fibroblasts from spinocerebellar ataxia type 3 (SCA3) patients. The disruption of this upregulation mitigates polyQ-induced neurodegeneration in Drosophila. We show that the transcriptional regulator Yin Yang 1 (YY1) associates with the Fuz promoter. Overexpression of YY1 promotes the hypermethylation of Fuz promoter, causing transcriptional repression of Fuz. Remarkably, YY1 protein is recruited to ATXN3-Q84 aggregates, which reduces the level of functional, soluble YY1, resulting in Fuz transcriptional derepression and induction of neuronal apoptosis. Furthermore, Fuz transcript level is elevated in amyloid beta-peptide, Tau and α-synuclein models, implicating its potential involvement in other neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Taken together, this study unveils a generic Fuz-mediated apoptotic cell death pathway in neurodegenerative disorders.
Persistent Identifierhttp://hdl.handle.net/10722/307240
ISSN
2023 Impact Factor: 6.5
2023 SCImago Journal Rankings: 3.193
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChen, Zhefan Stephen-
dc.contributor.authorLi, Li-
dc.contributor.authorPeng, Shaohong-
dc.contributor.authorChen, Francis M.-
dc.contributor.authorZhang, Qian-
dc.contributor.authorAn, Ying-
dc.contributor.authorLin, Xiao-
dc.contributor.authorLi, Wen-
dc.contributor.authorKoon, Alex Chun-
dc.contributor.authorChan, Ting Fung-
dc.contributor.authorLau, Kwok Fai-
dc.contributor.authorNgo, Jacky Chi Ki-
dc.contributor.authorWong, Wing Tak-
dc.contributor.authorKwan, Kin Ming-
dc.contributor.authorChan, Ho Yin Edwin-
dc.date.accessioned2021-11-03T06:22:12Z-
dc.date.available2021-11-03T06:22:12Z-
dc.date.issued2018-
dc.identifier.citationEMBO Reports, 2018, v. 19, n. 9, article no. e45409-
dc.identifier.issn1469-221X-
dc.identifier.urihttp://hdl.handle.net/10722/307240-
dc.description.abstractPlanar cell polarity (PCP) describes a cell–cell communication process through which individual cells coordinate and align within the plane of a tissue. In this study, we show that overexpression of Fuz, a PCP gene, triggers neuronal apoptosis via the dishevelled/Rac1 GTPase/MEKK1/JNK/caspase signalling axis. Consistent with this finding, endogenous Fuz expression is upregulated in models of polyglutamine (polyQ) diseases and in fibroblasts from spinocerebellar ataxia type 3 (SCA3) patients. The disruption of this upregulation mitigates polyQ-induced neurodegeneration in Drosophila. We show that the transcriptional regulator Yin Yang 1 (YY1) associates with the Fuz promoter. Overexpression of YY1 promotes the hypermethylation of Fuz promoter, causing transcriptional repression of Fuz. Remarkably, YY1 protein is recruited to ATXN3-Q84 aggregates, which reduces the level of functional, soluble YY1, resulting in Fuz transcriptional derepression and induction of neuronal apoptosis. Furthermore, Fuz transcript level is elevated in amyloid beta-peptide, Tau and α-synuclein models, implicating its potential involvement in other neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Taken together, this study unveils a generic Fuz-mediated apoptotic cell death pathway in neurodegenerative disorders.-
dc.languageeng-
dc.relation.ispartofEMBO Reports-
dc.subjectTau-
dc.subjectYin Yang 1-
dc.subjectpolyglutamine-
dc.subjectalpha-synuclein-
dc.subjectamyloid beta-peptide-
dc.titlePlanar cell polarity gene Fuz triggers apoptosis in neurodegenerative disease models-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.15252/embr.201745409-
dc.identifier.pmid30026307-
dc.identifier.pmcidPMC6123661-
dc.identifier.scopuseid_2-s2.0-85050803598-
dc.identifier.volume19-
dc.identifier.issue9-
dc.identifier.spagearticle no. e45409-
dc.identifier.epagearticle no. e45409-
dc.identifier.eissn1469-3178-
dc.identifier.isiWOS:000443682200005-

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