TY - JOUR
T1 - UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage- specific manner
AU - Ishikawa, Tokiro
AU - Toyama, Takuya
AU - Nakamura, Yuki
AU - Tamada, Kentaro
AU - Shimizu, Hitomi
AU - Ninagawa, Satoshi
AU - Okada, Tetsuya
AU - Kamei, Yasuhiro
AU - Ishikawa-Fujiwara, Tomoko
AU - Todo, Takeshi
AU - Aoyama, Eriko
AU - Takigawa, Masaharu
AU - Harada, Akihiro
AU - Mori, Kazutoshi
N1 - Funding Information:
We thank Ms. Kaoru Miyagawa and Ms. Yuki Okada for their technical and secretarial assistance. This work was financially supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26291040 and 17H01432 to K. Mori and 15K18529 and 17K15116 to T. Ishikawa). The authors declare no competing financial interests
Publisher Copyright:
© 2017 Ishikawa et al.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen. In this study, we show that this vacuolization step requires both ATF6 and BBF2H7 as UPR transducers and that BBF2H7 regulates a complete set of genes (Sec23/24/13/31, Tango1, Sedlin, and KLHL12) essential for the enlargement of COP II vesicles to accommodate long-chain collagen for export, leading to the formation of the perinotochordal basement membrane. Thus, the most appropriate UPR transducer is activated to cope with the differing physiological ER stresses of different content types depending on developmental stage.
AB - The unfolded protein response (UPR) handles unfolded/misfolded proteins accumulated in the endoplasmic reticulum (ER). However, it is unclear how vertebrates correctly use the total of ten UPR transducers. We have found that ER stress occurs physiologically during early embryonic development in medaka fish and that the smooth alignment of notochord cells requires ATF6 as a UPR transducer, which induces ER chaperones for folding of type VIII (short-chain) collagen. After secretion of hedgehog for tissue patterning, notochord cells differentiate into sheath cells, which synthesize type II collagen. In this study, we show that this vacuolization step requires both ATF6 and BBF2H7 as UPR transducers and that BBF2H7 regulates a complete set of genes (Sec23/24/13/31, Tango1, Sedlin, and KLHL12) essential for the enlargement of COP II vesicles to accommodate long-chain collagen for export, leading to the formation of the perinotochordal basement membrane. Thus, the most appropriate UPR transducer is activated to cope with the differing physiological ER stresses of different content types depending on developmental stage.
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U2 - 10.1083/jcb.201609100
DO - 10.1083/jcb.201609100
M3 - Article
C2 - 28500182
AN - SCOPUS:85021797146
VL - 216
SP - 1761
EP - 1774
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -