The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration.
The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration.
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DOI：
10.1007/s12035-018-1084-y
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发表时间：
2019-01
影响因子：
5.1
通讯作者：
Giorgini F
中科院分区：
文献类型：
--
作者：
Repici M;Hassanjani M;Maddison DC;Garção P;Cimini S;Patel B;Szegö ÉM;Straatman KR;Lilley KS;Borsello T;Outeiro TF;Panman L;Giorgini F
编码 DJ-1 的基因突变与常染色体隐性遗传的帕金森病 (PD) 相关。 DJ-1 在防止氧化应激方面发挥作用，但它如何作为“上游”氧化应激传感器发挥作用以及这是否与 PD 有关仍不清楚。有趣的是，DJ-1 可能作为一种 RNA 结合蛋白，与人脑中的特定 mRNA 转录物相关联。此外，我们之前报道过，酵母 DJ-1 同源物 Hsp31 在葡萄糖饥饿后定位于应激颗粒 (SG)，这表明 DJ-1 在 RNA 动力学中的作用。在这里，我们报告说，DJ-1 与哺乳动物细胞中的几种 SG 成分相互作用，并在诱导渗透或氧化应激时定位于 SG 以及 P 体。通过纯化哺乳动物细胞中与 DJ-1 相关的 mRNA，我们检测到了几个转录本，并发现这些转录本的亚群在应激后定位于 SG，这表明 DJ-1 可能将特定的 mRNA 靶向 mRNP 颗粒。值得注意的是，我们发现 DJ-1 与原代神经元中 N-甲基-d-天冬氨酸 (NMDA) 兴奋性毒性和多巴胺能细胞培养物中帕金森病诱导毒素产生的 SG 相关。因此，我们的结果表明 DJ-1 与应激和神经变性期间产生的细胞质 RNA 颗粒相关，这提供了 DJ-1 和 RNA 动力学之间可能的联系，这可能与 PD 发病机制相关。本文的在线版本 (10.1007/s12035-018-1084-y) 包含补充材料，可供授权用户使用。
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. The online version of this article (10.1007/s12035-018-1084-y) contains supplementary material, which is available to authorized users.
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影响因子：
7.8
作者：
Buchan, J. Ross;Muhlrad, Denise;Parker, Roy
通讯作者：
Parker, Roy
DOI：
10.1073/pnas.0902396106
发表时间：
2009-05-05
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Heutink, P
影响因子：
7
作者：
Ishihama, Y;Oda, Y;Mann, M
通讯作者：
Mann, M
影响因子：
8.6
作者：
Cookson, Mark R.
通讯作者：
Cookson, Mark R.