BROWSE

Related Researcher

Author's Photo

Lim, Chunghun
Neurogenetics & Ribonomics Laboratory (The Lim Lab)
Research Interests
  • Post-transcriptional Gene Expression, Neurodegeneration, Behavioral Genetics

ITEM VIEW & DOWNLOAD

Ataxin2 functions via CrebA to mediate Huntingtin toxicity in circadian clock neurons

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Ataxin2 functions via CrebA to mediate Huntingtin toxicity in circadian clock neurons
Author
Xu, FangkeKula-Eversole, ElzbietaIwanaszko, MartaLim, ChunghunAllada, Ravi
Issue Date
2019-10
Publisher
Public Library of Science
Citation
PLOS GENETICS, v.15, no.10, pp.e1008356
Abstract
Disrupted circadian rhythms is a prominent and early feature of neurodegenerative diseases including Huntington’s disease (HD). In HD patients and animal models, striatal and hypothalamic neurons expressing molecular circadian clocks are targets of mutant Huntingtin (mHtt) pathogenicity. Yet how mHtt disrupts circadian rhythms remains unclear. In a genetic screen for modifiers of mHtt effects on circadian behavior in Drosophila, we discovered a role for the neurodegenerative disease gene Ataxin2 (Atx2). Genetic manipulations of Atx2 modify the impact of mHtt on circadian behavior as well as mHtt aggregation and demonstrate a role for Atx2 in promoting mHtt aggregation as well as mHtt-mediated neuronal dysfunction. RNAi knockdown of the Fragile X mental retardation gene, dfmr1, an Atx2 partner, also partially suppresses mHtt effects and Atx2 effects depend on dfmr1. Atx2 knockdown reduces the cAMP response binding protein A (CrebA) transcript at dawn. CrebA transcript level shows a prominent diurnal regulation in clock neurons. Loss of CrebA also partially suppresses mHtt effects on behavior and cell loss and restoration of CrebA can suppress Atx2 effects. Our results indicate a prominent role of Atx2 in mediating mHtt pathology, specifically via its regulation of CrebA, defining a novel molecular pathway in HD pathogenesis.
URI
https://scholarworks.unist.ac.kr/handle/201301/27836
URL
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008356
DOI
10.1371/journal.pgen.1008356
ISSN
1553-7390
Appears in Collections:
SLS_Journal Papers
Files in This Item:
XuAllada2019PLoSGenet.pdf Download

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU