Planar cell polarity gene Fuz triggers apoptosis in neurodegenerative disease models

EMBO Reports
Zhefan Stephen ChenHo Yin Edwin Chan

Abstract

Planar 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...Continue Reading

References

Dec 10, 1999·Experimental Cell Research·E T Strovel, D J Sussman
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·J S SteffanL M Thompson
Mar 13, 2002·The EMBO Journal·Kay-Dietrich WagnerHolger Scholz
Jun 27, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yaohui ChaiHenry L Paulson
Nov 9, 2002·Bioinformatics·Long-Cheng Li, Rajvir Dahiya
Feb 25, 2003·Neuroreport·Chris Wing-Cheung LeePang-Chui Shaw
Mar 12, 2003·The EMBO Journal·Lakshmi AtchisonMichael L Atchison
Jun 25, 2004·Nucleic Acids Research·Albin SandelinBoris Lenhard
Aug 27, 2004·Brain : a Journal of Neurology·C M Everett, N W Wood
Jun 3, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cathy AndorferPeter Davies
Jul 26, 2005·Biochemical and Biophysical Research Communications·N Y Macy Huen, H Y Edwin Chan
Nov 14, 2006·Bioinformatics·Helge G RoiderMartin Vingron
Mar 31, 2007·Journal of Neurochemistry·Sandra RosasArturo Ortega
Apr 10, 2007·Annual Review of Neuroscience·Harry T Orr, Huda Y Zoghbi
Jun 2, 2007·Cell·Johannes L BosAlfred Wittinghofer
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
May 2, 2008·Nature·Ling-Bo LiNancy M Bonini
May 20, 2008·Journal of Neurochemistry·Ye He, Patrizia Casaccia-Bonnefil
Jun 19, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S L Alan WongH Y Edwin Chan
Oct 17, 2008·The Journal of Biological Chemistry·Kwok-Fai LauChristopher C J Miller
Mar 6, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Igor AllamanPierre J Magistretti
Jan 15, 2011·Genome Research·Aurélien A SérandourJérôme Eeckhoute
Mar 24, 2011·Nucleic Acids Research·Agnieszka FiszerWlodzimierz J Krzyzosiak
Aug 23, 2011·Molecular Neurodegeneration·Subbiah PugazhenthiChristopher B Eckman
Sep 13, 2011·PloS One·Melvin M EversWilleke M C van Roon-Mom
Feb 23, 2012·The Biochemical Journal·Wan Ning Vanessa ChowKwok-Fai Lau
Jul 6, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael P Hart, Aaron D Gitler
Aug 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ho TsoiHo Yin Edwin Chan

❮ Previous
Next ❯

Citations

Feb 26, 2019·Neural Regeneration Research·Zhefan Stephen Chen, Ho Yin Edwin Chan
Oct 27, 2020·Frontiers in Cell and Developmental Biology·Thijs C J VerheulTahsin Stefan Barakat
May 1, 2021·International Journal of Molecular Sciences·Virginie BotteroJudith A Potashkin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.