Rrs1 Is Involved in Endoplasmic Reticulum Stress Response in Huntington Disease
Rrs1 Is Involved in Endoplasmic Reticulum Stress Response in Huntington Disease
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DOI：
10.1074/jbc.m109.018325
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发表时间：
2009-07-03
影响因子：
4.8
通讯作者：
Persichetti, Francesca
中科院分区：
文献类型：
--
作者：
Carnemolla, Alisia;Fossale, Elisa;Persichetti, Francesca
Rrs 1表达的诱导是在亨廷顿病（HD）的症状前基因敲入小鼠模型中检测到的最早事件之一。Rrs 1上调符合HD标准的优势，纹状体特异性和多聚谷氨酰胺依赖。在这里，我们表明，哺乳动物Rrs 1是本地化的细胞核，以及在内质网（ER）的神经元。这种双重定位与其新鉴定的分子伴侣3D 3/lyric共享。然后，我们表明，这两个基因诱导的ER应激神经元。有趣的是，我们证明ER应激是症状前HD小鼠模型中的早期事件，其在啮齿动物的整个生命周期中持续存在。我们进一步表明，内质网应激也发生在HD患者的死后大脑。
The induction of Rrs1 expression is one of the earliest events detected in a presymptomatic knock-in mouse model of Huntington disease (HD). Rrs1 up-regulation fulfills the HD criteria of dominance, striatal specificity, and polyglutamine dependence. Here we show that mammalian Rrs1 is localized both in the nucleolus as well as in the endoplasmic reticulum ( ER) of neurons. This dual localization is shared with its newly identified molecular partner 3D3/lyric. We then show that both genes are induced by ER stress in neurons. Interestingly, we demonstrate that ER stress is an early event in a presymptomatic HD mouse model that persists throughout the life span of the rodent. We further show that ER stress also occurs in postmortem brains of HD patients.