| Title: | KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR |
| Authors: | Kamimura, Daisuke Browse this author →KAKEN DB |
| Katsunuma, Kokichi Browse this author |
| Arima, Yasunobu Browse this author |
| Atsumi, Toru Browse this author |
| Jiang, Jing-jing Browse this author |
| Bando, Hidenori Browse this author |
| Meng, Jie Browse this author |
| Sabharwal, Lavannya Browse this author |
| Stofkova, Andrea Browse this author |
| Nishikawa, Naoki Browse this author |
| Suzuki, Hironao Browse this author |
| Ogura, Hideki Browse this author →KAKEN DB |
| Ueda, Naoko Browse this author |
| Tsuruoka, Mineko Browse this author |
| Harada, Masaya Browse this author |
| Kobayashi, Junya Browse this author →KAKEN DB |
| Hasegawa, Takanori Browse this author |
| Yoshida, Hisahiro Browse this author →KAKEN DB |
| Koseki, Haruhiko Browse this author →KAKEN DB |
| Miura, Ikuo Browse this author →KAKEN DB |
| Wakana, Shigeharu Browse this author →KAKEN DB |
| Nishida, Keigo Browse this author →KAKEN DB |
| Kitamura, Hidemitsu Browse this author →KAKEN DB |
| Fukada, Toshiyuki Browse this author →KAKEN DB |
| Hirano, Toshio Browse this author →KAKEN DB |
| Murakami, Masaaki Browse this author →KAKEN DB |
| Issue Date: | Jun-2015 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Nature communications |
| Volume: | 6 |
| Start Page: | 7474 |
| Publisher DOI: | 10.1038/ncomms8474 |
| Abstract: | KDEL receptors are responsible for retrotransporting endoplasmic reticulum (ER) chaperones from the Golgi complex to the ER. Here we describe a role for KDEL receptor 1 (KDELR1) that involves the regulation of integrated stress responses (ISR) in T cells. Designing and using an N-ethyl-N-nitrosourea (ENU)-mutant mouse line, T-Red (naive T-cell reduced), we show that a point mutation in KDELR1 is responsible for the reduction in the number of naive T cells in this model owing to an increase in ISR. Mechanistic analysis shows that KDELR1 directly regulates protein phosphatase 1 (PP1), a key phosphatase for ISR in naive T cells. T-Red KDELR1 does not associate with PP1, resulting in reduced phosphatase activity against eIF2 alpha and subsequent expression of stress responsive genes including the proapoptotic factor Bim. These results demonstrate that KDELR1 regulates naive T-cell homeostasis by controlling ISR. |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/59745 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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