The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration

Abstract

Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.

Publication DOI: https://doi.org/10.1007/s12035-018-1084-y
Divisions: College of Health & Life Sciences
Additional Information: © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Uncontrolled Keywords: DJ-1,Parkinson’s disease,RNA-binding proteins,Stress granules,Neuroscience (miscellaneous),Neurology,Cellular and Molecular Neuroscience
Publication ISSN: 1559-1182
Last Modified: 28 Mar 2024 08:16
Date Deposited: 26 Mar 2019 08:51
Full Text Link:
Related URLs: https://link.sp ... 2035-018-1084-y (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-01-01
Published Online Date: 2018-04-19
Accepted Date: 2018-04-11
Authors: Repici, Mariaelena (ORCID Profile 0000-0002-9420-528X)
Hassanjani, Mahdieh
Maddison, Daniel C
Garção, Pedro
Cimini, Sara
Patel, Bhavini
Szegö, Éva M
Straatman, Kornelis R
Lilley, Kathryn S
Borsello, Tiziana
Outeiro, Tiago F
Panman, Lia
Giorgini, Flaviano

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