{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:33:31Z","timestamp":1790303611627,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Cell Biology (ASCB)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>ATF6\u03b1 and ATF6\u03b2 are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6\u03b1- and ATF6\u03b2 single-knockout mice develop normally, but ATF6\u03b1\/\u03b2 double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6\u03b1 is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6\u03b1\/\u03b2 double knockout, but not ATF6\u03b1- or ATF6\u03b2 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 ATF6\u03b1- and ATF6\u03b2-mediated induction of BiP, and that knockdown of the \u03b11 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6\u03b1\/\u03b2 double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6\u03b1\/\u03b2-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.<\/jats:p>","DOI":"10.1091\/mbc.e12-11-0830","type":"journal-article","created":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T16:33:23Z","timestamp":1362069203000},"page":"1387-1395","source":"Crossref","is-referenced-by-count":59,"title":["ATF6\u03b1\/\u03b2-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish"],"prefix":"10.1091","volume":"24","author":[{"given":"Tokiro","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan"},{"name":"CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan"},{"name":"CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Ishikawa-Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Todo","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Kamei","sequence":"additional","affiliation":[{"name":"Spectrography and Bioimaging Facility, National Institute for Basic Biology, Okazaki 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Shigenobu","sequence":"additional","affiliation":[{"name":"Functional Genomics Facility, National Institute for Basic Biology, Okazaki 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics for Reproduction, National Institute for Basic Biology, Okazaki 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro L.","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8561, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Sakaki","sequence":"additional","affiliation":[{"name":"RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Takeda","sequence":"additional","affiliation":[{"name":"CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan"},{"name":"Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutoshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan"},{"name":"CREST, Japan Science and Technology Corporation, Saitama 332-0012, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1247\/csf.07044","volume":"33","author":"Adachi Y","year":"2008","journal-title":"Cell Struct Funct"},{"key":"B2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cell.2006.04.014","volume":"125","author":"Bukau B","year":"2006","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"crossref","first-page":"18226","DOI":"10.1016\/S0021-9258(17)46834-7","volume":"268","author":"Chessler SD","year":"1993","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/0092-8674(93)90648-A","volume":"73","author":"Cox JS","year":"1993","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"crossref","first-page":"7947","DOI":"10.1074\/jbc.M110.156430","volume":"286","author":"Egawa N","year":"2011","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/jcb.240560412","volume":"56","author":"Ferreira LR","year":"1994","journal-title":"J Cell Biochem"},{"key":"B7","doi-asserted-by":"crossref","first-page":"10316","DOI":"10.1073\/pnas.1119273109","volume":"109","author":"Gade P","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"B8","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1002\/dvdy.21779","volume":"237","author":"Gansner JM","year":"2008","journal-title":"Dev Dyn"},{"key":"B9","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1002\/dvdy.21705","volume":"237","author":"Gansner JM","year":"2008","journal-title":"Dev Dyn"},{"key":"B10","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S1097-2765(00)00108-8","volume":"6","author":"Harding HP","year":"2000","journal-title":"Mol Cell"},{"key":"B11","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/S1097-2765(01)00264-7","volume":"7","author":"Harding HP","year":"2001","journal-title":"Mol Cell"},{"key":"B12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/16729","volume":"397","author":"Harding HP","year":"1999","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1042\/bj3550019","volume":"355","author":"Haze K","year":"2001","journal-title":"Biochem J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.11.3787"},{"key":"B15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1471-2199-11-70","volume":"11","author":"Ishikawa T","year":"2010","journal-title":"BMC Mol Biol"},{"key":"B16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1247\/csf.11036","volume":"36","author":"Ishikawa T","year":"2011","journal-title":"Cell Struct Funct"},{"key":"B17","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nature05846","volume":"447","author":"Kasahara M","year":"2007","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1002\/9780813818849","volume-title":"Medaka: Biology, Management, and Experimental Protocols","author":"Kinoshita M","year":"2009"},{"key":"B19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1006\/scdb.1999.0317","volume":"10","author":"Lamande SR","year":"1999","journal-title":"Semin Cell Dev Biol"},{"key":"B20","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1038\/sj.emboj.7600903","volume":"24","author":"Lee AH","year":"2005","journal-title":"EMBO J"},{"key":"B21","doi-asserted-by":"crossref","first-page":"5688","DOI":"10.1128\/MCB.00779-06","volume":"26","author":"Luo S","year":"2006","journal-title":"Mol Cell Biol"},{"key":"B22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0092-8674(00)80855-7","volume":"101","author":"Mori K","year":"2000","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1093\/jb\/mvp166","volume":"146","author":"Mori K","year":"2009","journal-title":"J Biochem"},{"key":"B24","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0092-8674(93)90521-Q","volume":"74","author":"Mori K","year":"1993","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-09-0693"},{"key":"B26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.semcdb.2003.09.020","volume":"14","author":"Nagata K","year":"2003","journal-title":"Semin Cell Dev Biol"},{"key":"B27","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/0092-8674(89)90059-7","volume":"57","author":"Normington K","year":"1989","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"crossref","first-page":"31024","DOI":"10.1074\/jbc.M300923200","volume":"278","author":"Okada T","year":"2003","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1042\/bj20020391","volume":"366","author":"Okada T","year":"2002","journal-title":"Biochem J"},{"key":"B30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ydbio.2007.12.033","volume":"316","author":"Pagnon-Minot A","year":"2008","journal-title":"Dev Biol"},{"key":"B31","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1242\/dev.129.13.3137","volume":"129","author":"Parsons MJ","year":"2002","journal-title":"Development"},{"key":"B32","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1101\/gad.14.2.152","volume":"14","author":"Reimold AM","year":"2000","journal-title":"Genes Dev"},{"key":"B33","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/35085509","volume":"412","author":"Reimold AM","year":"2001","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/0092-8674(89)90058-5","volume":"57","author":"Rose MD","year":"1989","journal-title":"Cell"},{"key":"B35","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1242\/dev.116.4.1021","volume":"116","author":"Schulte-Merker S","year":"1992","journal-title":"Development"},{"key":"B36","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1126\/science.1209235","volume":"334","author":"Smith MH","year":"2011","journal-title":"Science"},{"key":"B37","doi-asserted-by":"crossref","first-page":"R116","DOI":"10.1186\/gb-2006-7-12-r116","volume":"7","author":"Taniguchi Y","year":"2006","journal-title":"Genome Biol"},{"key":"B38","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.metabol.2012.01.004","volume":"61","author":"Usui M","year":"2012","journal-title":"Metabolism"},{"key":"B39","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","volume":"334","author":"Walter P","year":"2011","journal-title":"Science"},{"key":"B40","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/343657a0","volume":"343","author":"Wilkinson DG","year":"1990","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"crossref","first-page":"9637","DOI":"10.1074\/jbc.273.16.9637","volume":"273","author":"Wilson R","year":"1998","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cmet.2011.01.003","volume":"13","author":"Wu J","year":"2011","journal-title":"Cell Metab"},{"key":"B43","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.devcel.2007.07.005","volume":"13","author":"Wu J","year":"2007","journal-title":"Dev Cell"},{"key":"B44","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.devcel.2007.07.018","volume":"13","author":"Yamamoto K","year":"2007","journal-title":"Dev Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-02-0133"},{"key":"B46","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S1097-2765(00)00133-7","volume":"6","author":"Ye J","year":"2000","journal-title":"Mol Cell"},{"key":"B47","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1534-5807(03)00022-4","volume":"4","author":"Yoshida H","year":"2003","journal-title":"Dev Cell"},{"key":"B48","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","volume":"107","author":"Yoshida H","year":"2001","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1128\/MCB.20.18.6755-6767.2000","volume":"20","author":"Yoshida H","year":"2000","journal-title":"Mol Cell Biol"},{"key":"B50","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1128\/MCB.21.4.1239-1248.2001","volume":"21","author":"Yoshida H","year":"2001","journal-title":"Mol Cell Biol"},{"key":"B51","doi-asserted-by":"crossref","first-page":"7064","DOI":"10.1074\/jbc.M708530200","volume":"283","author":"Zhou D","year":"2008","journal-title":"J Biol Chem"}],"container-title":["Molecular Biology of the Cell"],"original-title":[],"language":"en","deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T17:41:09Z","timestamp":1644428469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.molbiolcell.org\/doi\/10.1091\/mbc.e12-11-0830"}},"subtitle":[],"editor":[{"given":"Jeffrey L.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1091\/mbc.e12-11-0830"],"URL":"https:\/\/doi.org\/10.1091\/mbc.e12-11-0830","relation":{},"ISSN":["1059-1524","1939-4586"],"issn-type":[{"value":"1059-1524","type":"print"},{"value":"1939-4586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5]]}}}