Murakami T, Hino S-I, Saito A, Imaizumi K
Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan.
Neuroscience. 2007 Apr 25;146(1):1-8. doi: 10.1016/j.neuroscience.2007.01.069. Epub 2007 Mar 23.
The endoplasmic reticulum (ER) is an organelle in which secretory and transmembrane proteins are folded or processed, and is susceptible to various stresses that provoke the accumulation of unfolded proteins in the ER lumen. Recently, ER stress has been reported to be linked to neuronal death in various neurodegenerative diseases. Neurons contain the ER not only in the soma, but also in the dendrites, thus presenting a different case to non-neuronal cells. The ER in the dendrites has potential functions in local protein synthesis and sorting of synthesized proteins to postsynaptic membranes. It raises the possibility that ER stress could occur locally in the dendrites. Here we showed that ER stress sensors, inositol-requiring 1 (IRE1), PKR-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) exist in the ER of both soma and dendrites in primary mouse neurons, and that under ER stress conditions, GRP78/BiP and phosphorylated eIF2alpha are induced. Furthermore, XBP1 mRNA was localized in the proximal dendrites where IRE1 was rapidly phosphorylated in response to ER stress. These results indicate that the ER in dendrites could respond to ER stress and retain the capacity of protein quality control.
内质网（ER）是一种细胞器，分泌蛋白和跨膜蛋白在此折叠或加工，并且易受各种应激影响，这些应激会导致内质网腔中未折叠蛋白的积累。最近有报道称，内质网应激与多种神经退行性疾病中的神经元死亡有关。神经元不仅在胞体中含有内质网，在树突中也含有内质网，因此与非神经元细胞情况不同。树突中的内质网在局部蛋白质合成以及将合成的蛋白质分选到突触后膜方面具有潜在功能。这增加了内质网应激可能在树突中局部发生的可能性。在此我们表明，内质网应激传感器，即肌醇需求酶1（IRE1）、蛋白激酶R样内质网激酶（PERK）和激活转录因子6（ATF6）存在于原代小鼠神经元胞体和树突的内质网中，并且在内质网应激条件下，会诱导葡萄糖调节蛋白78/免疫球蛋白重链结合蛋白（GRP78/BiP）和磷酸化真核翻译起始因子2α（eIF2α）。此外，X盒结合蛋白1（XBP1）mRNA定位于近端树突，在那里IRE1会因内质网应激而迅速磷酸化。这些结果表明，树突中的内质网能够对内质网应激做出反应并保留蛋白质质量控制的能力。
