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

Daisuke Kamimura; Kokichi Katsunuma; Yasunobu Arima; Toru Atsumi; Jing Jing Jiang; Hidenori Bando; Jie Meng; Lavannya Sabharwal; Andrea Stofkova; Naoki Nishikawa; Hironao Suzuki; Hideki Ogura; Naoko Ueda; Mineko Tsuruoka; Masaya Harada; Junya Kobayashi; Takanori Hasegawa; Hisahiro Yoshida; Haruhiko Koseki; Ikuo Miura; Shigeharu Wakana; Keigo Nishida; Hidemitsu Kitamura; Toshiyuki Fukada; Toshio Hirano; Masaaki Murakami

doi:10.1038/ncomms8474

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

Daisuke Kamimura, Kokichi Katsunuma, Yasunobu Arima, Toru Atsumi, Jing Jing Jiang, Hidenori Bando, Jie Meng, Lavannya Sabharwal, Andrea Stofkova, Naoki Nishikawa, Hironao Suzuki, Hideki Ogura, Naoko Ueda, Mineko Tsuruoka, Masaya Harada, Junya Kobayashi, Takanori Hasegawa, Hisahiro Yoshida, Haruhiko Koseki, Ikuo MiuraShigeharu Wakana, Keigo Nishida, Hidemitsu Kitamura, Toshiyuki Fukada, Toshio Hirano, Masaaki Murakami

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

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 (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.

Original language	English
Article number	7474
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8474
Publication status	Published - 17-06-2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms8474

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Kamimura, D., Katsunuma, K., Arima, Y., Atsumi, T., Jiang, J. J., Bando, H., Meng, J., Sabharwal, L., Stofkova, A., Nishikawa, N., Suzuki, H., Ogura, H., Ueda, N., Tsuruoka, M., Harada, M., Kobayashi, J., Hasegawa, T., Yoshida, H., Koseki, H., ... Murakami, M. (2015). KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR. Nature communications, 6, Article 7474. https://doi.org/10.1038/ncomms8474

@article{4a80a1f75ff84c618e123c3c05a9c732,

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

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 (na{\"i}ve T-cell reduced), we show that a point mutation in KDELR1 is responsible for the reduction in the number of na{\"i}ve 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 na{\"i}ve 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 na{\"i}ve T-cell homeostasis by controlling ISR.",

author = "Daisuke Kamimura and Kokichi Katsunuma and Yasunobu Arima and Toru Atsumi and Jiang, {Jing Jing} and Hidenori Bando and Jie Meng and Lavannya Sabharwal and Andrea Stofkova and Naoki Nishikawa and Hironao Suzuki and Hideki Ogura and Naoko Ueda and Mineko Tsuruoka and Masaya Harada and Junya Kobayashi and Takanori Hasegawa and Hisahiro Yoshida and Haruhiko Koseki and Ikuo Miura and Shigeharu Wakana and Keigo Nishida and Hidemitsu Kitamura and Toshiyuki Fukada and Toshio Hirano and Masaaki Murakami",

year = "2015",

month = jun,

day = "17",

doi = "10.1038/ncomms8474",

language = "English",

volume = "6",

journal = "Nature communications",

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Kamimura, D, Katsunuma, K, Arima, Y, Atsumi, T, Jiang, JJ, Bando, H, Meng, J, Sabharwal, L, Stofkova, A, Nishikawa, N, Suzuki, H, Ogura, H, Ueda, N, Tsuruoka, M, Harada, M, Kobayashi, J, Hasegawa, T, Yoshida, H, Koseki, H, Miura, I, Wakana, S, Nishida, K, Kitamura, H, Fukada, T, Hirano, T & Murakami, M 2015, 'KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR', Nature communications, vol. 6, 7474. https://doi.org/10.1038/ncomms8474

TY - JOUR

T1 - KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR

AU - Kamimura, Daisuke

AU - Katsunuma, Kokichi

AU - Arima, Yasunobu

AU - Atsumi, Toru

AU - Jiang, Jing Jing

AU - Bando, Hidenori

AU - Meng, Jie

AU - Sabharwal, Lavannya

AU - Stofkova, Andrea

AU - Nishikawa, Naoki

AU - Suzuki, Hironao

AU - Ogura, Hideki

AU - Ueda, Naoko

AU - Tsuruoka, Mineko

AU - Harada, Masaya

AU - Kobayashi, Junya

AU - Hasegawa, Takanori

AU - Yoshida, Hisahiro

AU - Koseki, Haruhiko

AU - Miura, Ikuo

AU - Wakana, Shigeharu

AU - Nishida, Keigo

AU - Kitamura, Hidemitsu

AU - Fukada, Toshiyuki

AU - Hirano, Toshio

AU - Murakami, Masaaki

PY - 2015/6/17

Y1 - 2015/6/17

N2 - 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.

AB - 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.

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U2 - 10.1038/ncomms8474

DO - 10.1038/ncomms8474

M3 - Article

C2 - 26081938

AN - SCOPUS:84935871697

SN - 2041-1723

VL - 6

JO - Nature communications

JF - Nature communications

M1 - 7474

ER -

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

Abstract

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