UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner

The Journal of Cell Biology
Tokiro IshikawaKazutoshi Mori

Abstract

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, andKLHL12) essential for the enlargement of COPII 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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Citations

Aug 16, 2018·Annual Review of Cell and Developmental Biology·Eugene OhMichael Rape
Nov 7, 2018·Cold Spring Harbor Perspectives in Biology·Steffen Preissler, David Ron
Jun 22, 2019·Disease Models & Mechanisms·Gianluca D'AgatiAlexa Burger
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Aug 21, 2020·Molecular and Cellular Biochemistry·Kentaro Oh-HashiYoko Hirata
Jun 1, 2018·G3 : Genes - Genomes - Genetics·Tokiro IshikawaKazutoshi Mori
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Methods Mentioned

BETA
transgenic
Fluorescence
Confocal microscopy
electron microscopy
transfection
PCR
in vitro transcription
Assay

Software Mentioned

Ensemble Genome Browser
Las AF

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