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Title: ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.
Authors: Ishikawa, Tokiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Okada, Tetsuya  kyouindb  KAKEN_id
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  kyouindb  KAKEN_id
Mori, Kazutoshi  kyouindb  KAKEN_id
Author's alias: 森, 和俊
Issue Date: May-2013
Publisher: American Society for Cell Biology
Journal title: Molecular biology of the cell
Volume: 24
Issue: 9
Start page: 1387
End page: 1395
Abstract: 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.
Rights: © 2013 by The American Society for Cell Biology.
DOI(Published Version): 10.1091/mbc.E12-11-0830
PubMed ID: 23447699
Appears in Collections:Journal Articles

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