Mislocalization to the nuclear envelope: An effect of the dystonia-causing torsinA mutation
Mislocalization to the nuclear envelope: An effect of the dystonia-causing torsinA mutation
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DOI：
10.1073/pnas.0304375101
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发表时间：
2004-01-20
影响因子：
11.1
通讯作者：
Dauer, WT
中科院分区：
文献类型：
--
作者：
Goodchild, RE;Dauer, WT
原发性肌张力障碍是一种以中枢神经系统功能障碍引起的不自主扭转运动为特征的疾病，无潜在的组织病理学。DYT1肌张力障碍是由编码内质网腔蛋白torsinA的TOR1A基因中的符合读码框的GAG缺失（DeltaE302/3）引起的原发性肌张力障碍的一种形式。我们发现，torsinA也存在于核膜（NE），在那里它似乎与底物相互作用，和DeltaE302/3突变导致一个显着的重新分配torsinA从内质网到NE。此外，DeltaE302/3-torsinA将WT torsinA招募到NE，可能为理解该疾病的显性遗传提供了深入了解。DYT1肌张力障碍似乎是一种以前没有特征的NE疾病，据我们所知，它是第一种选择性影响CNS功能的疾病。
Primary dystonia is a disease characterized by involuntary twisting movements caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a form of primary dystonia caused by an in-frame GAG deletion (DeltaE302/3) in the TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We show that torsinA is also present in the nuclear envelope (NE), where it appears to interact with substrate, and that the DeltaE302/3 mutation causes a striking redistribution of torsinA from the endoplasmic reticulum to the NE. In addition, DeltaE302/3-torsinA recruits WT torsinA to the NE, potentially providing insight into an understanding of the dominant inheritance of the disease. DYT1 dystonia appears to be a previously uncharacterized NE disease and the first, to our knowledge, to selectively affect CNS function.