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ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryon...

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Autores principales: Ishikawa, Tokiro, Okada, Tetsuya, Ishikawa-Fujiwara, Tomoko, Todo, Takeshi, Kamei, Yasuhiro, Shigenobu, Shuji, Tanaka, Minoru, Saito, Taro L., Yoshimura, Jun, Morishita, Shinichi, Toyoda, Atsushi, Sakaki, Yoshiyuki, Taniguchi, Yoshihito, Takeda, Shunichi, Mori, Kazutoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639050/
https://www.ncbi.nlm.nih.gov/pubmed/23447699
http://dx.doi.org/10.1091/mbc.E12-11-0830
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author Ishikawa, Tokiro
Okada, Tetsuya
Ishikawa-Fujiwara, Tomoko
Todo, Takeshi
Kamei, Yasuhiro
Shigenobu, Shuji
Tanaka, Minoru
Saito, Taro L.
Yoshimura, Jun
Morishita, Shinichi
Toyoda, Atsushi
Sakaki, Yoshiyuki
Taniguchi, Yoshihito
Takeda, Shunichi
Mori, Kazutoshi
author_facet Ishikawa, Tokiro
Okada, Tetsuya
Ishikawa-Fujiwara, Tomoko
Todo, Takeshi
Kamei, Yasuhiro
Shigenobu, Shuji
Tanaka, Minoru
Saito, Taro L.
Yoshimura, Jun
Morishita, Shinichi
Toyoda, Atsushi
Sakaki, Yoshiyuki
Taniguchi, Yoshihito
Takeda, Shunichi
Mori, Kazutoshi
author_sort Ishikawa, Tokiro
collection PubMed
description ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra.
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spelling pubmed-36390502013-07-16 ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish Ishikawa, Tokiro Okada, Tetsuya Ishikawa-Fujiwara, Tomoko Todo, Takeshi Kamei, Yasuhiro Shigenobu, Shuji Tanaka, Minoru Saito, Taro L. Yoshimura, Jun Morishita, Shinichi Toyoda, Atsushi Sakaki, Yoshiyuki Taniguchi, Yoshihito Takeda, Shunichi Mori, Kazutoshi Mol Biol Cell Articles ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra. The American Society for Cell Biology 2013-05-01 /pmc/articles/PMC3639050/ /pubmed/23447699 http://dx.doi.org/10.1091/mbc.E12-11-0830 Text en © 2013 Ishikawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Ishikawa, Tokiro
Okada, Tetsuya
Ishikawa-Fujiwara, Tomoko
Todo, Takeshi
Kamei, Yasuhiro
Shigenobu, Shuji
Tanaka, Minoru
Saito, Taro L.
Yoshimura, Jun
Morishita, Shinichi
Toyoda, Atsushi
Sakaki, Yoshiyuki
Taniguchi, Yoshihito
Takeda, Shunichi
Mori, Kazutoshi
ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title_full ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title_fullStr ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title_full_unstemmed ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title_short ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish
title_sort atf6α/β-mediated adjustment of er chaperone levels is essential for development of the notochord in medaka fish
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639050/
https://www.ncbi.nlm.nih.gov/pubmed/23447699
http://dx.doi.org/10.1091/mbc.E12-11-0830
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