|
ウシオダ リョウ
USHIODA RYO
潮田 亮 所属 京都産業大学 生命科学部 先端生命科学科 職種 准教授 |
|
| 発行・発表の年月 | 2016/10/11 |
| 形態種別 | 研究論文 |
| 標題 | Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by disulfide reductase ERdj5 |
| 執筆形態 | その他 |
| 掲載誌名 | Proceedings of the National Academy of Sciences |
| 出版社・発行元 | Proceedings of the National Academy of Sciences |
| 巻・号・頁 | 113(41),E6055-E6063頁 |
| 著者・共著者 | Ryo Ushioda,Akitoshi Miyamoto,Michio Inoue,Satoshi Watanabe,Masaki Okumura,Ken-ichi Maegawa,Kaiku Uegaki,Shohei Fujii,Yasuko Fukuda,Masataka Umitsu,Junichi Takagi,Kenji Inaba,Katsuhiko Mikoshiba,Kazuhiro Nagata |
| 概要 | Calcium ion (Ca2+) is an important second messenger that regulates numerous cellular functions. Intracellular Ca2+ concentration ([Ca2+]i) is strictly controlled by Ca2+ channels and pumps on the endoplasmic reticulum (ER) and plasma membranes. The ER calcium pump, sarco/endoplasmic reticulum calcium ATPase (SERCA), imports Ca2+ from the cytosol into the ER in an ATPase activity-dependent manner. The activity of SERCA2b, the ubiquitous isoform of SERCA, is negatively regulated by disulfide bond formation between two luminal cysteines. Here, we show that ERdj5, a mammalian ER disulfide reductase, which we reported to be involved in the ER-associated degradation of misfolded proteins, activates the pump function of SERCA2b by reducing its luminal disulfide bond. Notably, ERdj5 activated SERCA2b at a lower ER luminal [Ca2+] ([Ca2+]ER), whereas a higher [Ca2+]ER induced ERdj5 to form oligomers that were no longer able to interact with the pump, suggesting [Ca2+]ER-dependent regulation. Binding Ig protein, an ER-resident molecular chaperone, exerted a regulatory role in the oligomerization by binding to the J domain of ERdj5. These results identify ERdj5 as one of the master regulators of ER calcium homeostasis and thus shed light on the importance of cross talk among redox, Ca2+, and protein homeostasis in the ER. |
| DOI | 10.1073/pnas.1605818113 |
| ISSN | 0027-8424/1091-6490 |
| PermalinkURL | http://www.pnas.org/syndication/doi/10.1073/pnas.1605818113 |
| researchmap用URL | https://syndication.highwire.org/content/doi/10.1073/pnas.1605818113 |