演題詳細
Poster
アルギニンメチル化が及ぼす細胞内オルガネラへの影響
Effect of arginine methylation via PRMT1 on organella
- P3-389
- 松崎 伸介 / Shinsuke Matsuzaki:1,2,3 三好 耕 / KO MIYOSHI:1,3 森 泰丈 / YASUTAKE MORI:2 片山 泰一 / TAIICHI KATAYAMA:1
- 1:大阪大学大学院・連合小児発達学研究科・分子生物遺伝学 / Dept. of Mol. Brain Sci., United Grad. Sch. of Child Development, Osaka Univ., Osaka, Japan 2:大阪大学大学院・医学系研究科・神経機能形態学講座 / Dept of Anatomy and Neurosci., Grad. Sch. of Med., Osaka University, Osaka, Japan 3:大阪大学大学・院連合小児発達学研究科・子どものこころの分子統御機構研究センター / Molecular Research Center for Children's Mental Development, United Grad. Sch. of Child Development, Osaka Univ., Osaka, Japan
Cumulative of reports have shown the importance of ER stress in pathology of neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, etc. These studies indicate that the cellular events in response to ER stress should relate to the pathology of neurodegenerative diseases. To this aim, we investigated the altered genes in SK-N-SH cells in the condition of tunicamycin-induced ER stress by gene fishing method. As the result, we found that Protein arginine N-methyltransferase 1, PRMT1, is up-regulated in SK-N-SH cells under ER stress. Based on this result, we addressed the following issues;
1: Can ER stress increase the protein level of PRMT1?
2: What kind of ER stress pathways is involve in the expression of PRMT1?
3: Can ER stress affect the localization of PRMT1?
Our results elucidated that several ER stress pathways induced PRMT1 expression, some of which affected the subcellular localization of PRMT1. Next, to examine the function of PRMT1 in the ER stress response, we downregulated the expression of PRMT1 by RNAi. When we analysed the organelle localization and function in the PRMT1 knockdown cells, the localization of Golgi apparatus was altered and the induction of GRP78 by tunicamycin was severely impaired. These results suggested a novel pathway via protein methylation that mediates organelle stress to the nucleus, possibly involved in the pathogenesis of neurodegenerative diseases.