Ueda Masashi, Li Shimo, Itoh Masanori, Wang Miao-Xing, Hayakawa Miki, Islam Saiful, Nakagawa Kiyomi, Chen Huayue, Nakagawa Toshiyuki
Department of Neurobiology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Department of Anatomy, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Biochem Biophys Res Commun. 2016 May 27;474(2):259-263. doi: 10.1016/j.bbrc.2016.04.034. Epub 2016 Apr 11.
The endoplasmic reticulum (ER) is important in various cellular functions, such as secretary and membrane protein biosynthesis, lipid synthesis, and calcium storage. ER stress, including membrane distortion, is associated with many diseases such as Huntington's disease. In particular, nuclear envelope distortion is related to neuronal cell death associated with polyglutamine. However, the mechanism by which polyglutamine causes ER membrane distortion remains unclear. We used electron microscopy, fluorescence protease protection assay, and alkaline treatment to analyze the localization of polyglutamine in cells. We characterized polyglutamine embedded in the ER membrane and noted an effect on morphology, including the dilation of ER luminal space and elongation of ER-mitochondria contact sites, in addition to the distortion of the nuclear envelope. The polyglutamine embedded in the ER membrane was observed at the same time as Bax insertion. These results demonstrated that the ER membrane may be a target of polyglutamine, which triggers cell death through Bax.
内质网（ER）在多种细胞功能中发挥着重要作用，例如分泌蛋白和膜蛋白的生物合成、脂质合成以及钙储存。内质网应激，包括膜变形，与许多疾病相关，如亨廷顿舞蹈症。特别是，核膜变形与多聚谷氨酰胺相关的神经元细胞死亡有关。然而，多聚谷氨酰胺导致内质网膜变形的机制仍不清楚。我们使用电子显微镜、荧光蛋白酶保护测定法和碱性处理来分析多聚谷氨酰胺在细胞中的定位。我们对嵌入内质网膜的多聚谷氨酰胺进行了表征，并注意到其对形态的影响，除了核膜变形外，还包括内质网腔空间的扩张和内质网与线粒体接触位点的延长。在观察到Bax插入的同时，也观察到了嵌入内质网膜的多聚谷氨酰胺。这些结果表明，内质网膜可能是多聚谷氨酰胺的靶点，多聚谷氨酰胺通过Bax触发细胞死亡。
