Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/42121
Title: The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration.
Authors: Repici, Mariaelena
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
First Published: 19-Apr-2018
Publisher: Humana Press
Citation: Molecular Neurobiology, 2018, pp. 1-17
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.
DOI Link: 10.1007/s12035-018-1084-y
ISSN: 0893-7648
eISSN: 1559-1182
Links: https://link.springer.com/article/10.1007%2Fs12035-018-1084-y
http://hdl.handle.net/2381/42121
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Biology

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