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

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...

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Autores principales: Kamimura, Daisuke, Katsunuma, Kokichi, Arima, Yasunobu, Atsumi, Toru, Jiang, Jing-jing, Bando, Hidenori, Meng, Jie, Sabharwal, Lavannya, Stofkova, Andrea, Nishikawa, Naoki, Suzuki, Hironao, Ogura, Hideki, Ueda, Naoko, Tsuruoka, Mineko, Harada, Masaya, Kobayashi, Junya, Hasegawa, Takanori, Yoshida, Hisahiro, Koseki, Haruhiko, Miura, Ikuo, Wakana, Shigeharu, Nishida, Keigo, Kitamura, Hidemitsu, Fukada, Toshiyuki, Hirano, Toshio, Murakami, Masaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557295/
https://www.ncbi.nlm.nih.gov/pubmed/26081938
http://dx.doi.org/10.1038/ncomms8474
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author Kamimura, Daisuke
Katsunuma, Kokichi
Arima, Yasunobu
Atsumi, Toru
Jiang, Jing-jing
Bando, Hidenori
Meng, Jie
Sabharwal, Lavannya
Stofkova, Andrea
Nishikawa, Naoki
Suzuki, Hironao
Ogura, Hideki
Ueda, Naoko
Tsuruoka, Mineko
Harada, Masaya
Kobayashi, Junya
Hasegawa, Takanori
Yoshida, Hisahiro
Koseki, Haruhiko
Miura, Ikuo
Wakana, Shigeharu
Nishida, Keigo
Kitamura, Hidemitsu
Fukada, Toshiyuki
Hirano, Toshio
Murakami, Masaaki
author_facet Kamimura, Daisuke
Katsunuma, Kokichi
Arima, Yasunobu
Atsumi, Toru
Jiang, Jing-jing
Bando, Hidenori
Meng, Jie
Sabharwal, Lavannya
Stofkova, Andrea
Nishikawa, Naoki
Suzuki, Hironao
Ogura, Hideki
Ueda, Naoko
Tsuruoka, Mineko
Harada, Masaya
Kobayashi, Junya
Hasegawa, Takanori
Yoshida, Hisahiro
Koseki, Haruhiko
Miura, Ikuo
Wakana, Shigeharu
Nishida, Keigo
Kitamura, Hidemitsu
Fukada, Toshiyuki
Hirano, Toshio
Murakami, Masaaki
author_sort Kamimura, Daisuke
collection PubMed
description 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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spelling pubmed-45572952015-09-11 KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR Kamimura, Daisuke Katsunuma, Kokichi Arima, Yasunobu Atsumi, Toru Jiang, Jing-jing Bando, Hidenori Meng, Jie Sabharwal, Lavannya Stofkova, Andrea Nishikawa, Naoki Suzuki, Hironao Ogura, Hideki Ueda, Naoko Tsuruoka, Mineko Harada, Masaya Kobayashi, Junya Hasegawa, Takanori Yoshida, Hisahiro Koseki, Haruhiko Miura, Ikuo Wakana, Shigeharu Nishida, Keigo Kitamura, Hidemitsu Fukada, Toshiyuki Hirano, Toshio Murakami, Masaaki Nat Commun Article 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. Nature Pub. Group 2015-06-17 /pmc/articles/PMC4557295/ /pubmed/26081938 http://dx.doi.org/10.1038/ncomms8474 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kamimura, Daisuke
Katsunuma, Kokichi
Arima, Yasunobu
Atsumi, Toru
Jiang, Jing-jing
Bando, Hidenori
Meng, Jie
Sabharwal, Lavannya
Stofkova, Andrea
Nishikawa, Naoki
Suzuki, Hironao
Ogura, Hideki
Ueda, Naoko
Tsuruoka, Mineko
Harada, Masaya
Kobayashi, Junya
Hasegawa, Takanori
Yoshida, Hisahiro
Koseki, Haruhiko
Miura, Ikuo
Wakana, Shigeharu
Nishida, Keigo
Kitamura, Hidemitsu
Fukada, Toshiyuki
Hirano, Toshio
Murakami, Masaaki
KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title_full KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title_fullStr KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title_full_unstemmed KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title_short KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR
title_sort kdel receptor 1 regulates t-cell homeostasis via pp1 that is a key phosphatase for isr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557295/
https://www.ncbi.nlm.nih.gov/pubmed/26081938
http://dx.doi.org/10.1038/ncomms8474
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