KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
| Autor: | Yasunobu Arima, Jie Meng, Ikuo Miura, Shigeharu Wakana, Hisahiro Yoshida, Toru Atsumi, Junya Kobayashi, Andrea Stofkova, Hironao Suzuki, Daisuke Kamimura, Hidemitsu Kitamura, Jing-Jing Jiang, Haruhiko Koseki, Kokichi Katsunuma, Naoko Ueda, Naoki Nishikawa, Masaaki Murakami, Hideki Ogura, Hidenori Bando, Toshio Hirano, Toshiyuki Fukada, Takanori Hasegawa, Lavannya Sabharwal, Masaya Harada, Keigo Nishida, Mineko Tsuruoka |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Receptors
Peptide KDEL T-Lymphocytes Phosphatase Eukaryotic Initiation Factor-2 Molecular Sequence Data Immunology General Physics and Astronomy Biology General Biochemistry Genetics and Molecular Biology Article symbols.namesake Stress Physiological Protein Phosphatase 1 Proto-Oncogene Proteins Animals Homeostasis Point Mutation Amino Acid Sequence Receptor Mice Knockout Mice Inbred C3H Multidisciplinary Bcl-2-Like Protein 11 KDELR1 Endoplasmic reticulum Membrane Proteins Protein phosphatase 1 General Chemistry Golgi apparatus Cell biology Mice Inbred C57BL Biological sciences Phenotype symbols Female Apoptosis Regulatory Proteins Immunologic Memory |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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 (naïve T-cell reduced), we show that a point mutation in KDELR1 is responsible for the reduction in the number of naïve 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 naïve T cells. T-Red KDELR1 does not associate with PP1, resulting in reduced phosphatase activity against eIF2α and subsequent expression of stress responsive genes including the proapoptotic factor Bim. These results demonstrate that KDELR1 regulates naïve T-cell homeostasis by controlling ISR. KDEL receptors are known to be involved in retrotransporting chaperones to the endoplasmic reticulum from the Golgi complex. Here the authors unravel a role of KDEL receptor 1 in regulating integrated stress responses in naïve T cells through its association with protein phosphatase 1. |
| Databáze: | OpenAIRE |
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