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KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR

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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.
Type: article
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)

Submitter: 上村 大輔

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