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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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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. |
format | Online Article Text |
id | pubmed-3639050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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