Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.

IRE1, an ER-localized transmembrane protein, plays a central role in the unfolded protein response (UPR). IRE1 senses the accumulation of unfolded proteins in its luminal domain and transmits a signal to the cytosolic side through its kinase and RNase domains. Although the downstream pathways mediat...

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Autores principales:	Daisuke Oikawa, Akira Kitamura, Masataka Kinjo, Takao Iwawaki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8657280c05bf4234a941f93245d332ba
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spelling	oai:doaj.org-article:8657280c05bf4234a941f93245d332ba2021-11-18T08:05:57ZDirect association of unfolded proteins with mammalian ER stress sensor, IRE1β.1932-620310.1371/journal.pone.0051290https://doaj.org/article/8657280c05bf4234a941f93245d332ba2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23236464/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203IRE1, an ER-localized transmembrane protein, plays a central role in the unfolded protein response (UPR). IRE1 senses the accumulation of unfolded proteins in its luminal domain and transmits a signal to the cytosolic side through its kinase and RNase domains. Although the downstream pathways mediated by two mammalian IRE1s, IRE1α and IRE1β, are well documented, their luminal events have not been fully elucidated. In particular, there have been no reports on how IRE1β senses the unfolded proteins. In this study, we performed a comparative analysis to clarify the luminal event mediated by the mammalian IRE1s. Confocal fluorescent microscopy using GFP-fused IRE1s revealed that IRE1β clustered into discrete foci upon ER stress. Also, fluorescence correlation spectroscopy (FCS) analysis in living cells indicated that the size of the IRE1β complex is robustly increased upon ER stress. Moreover, unlike IRE1α, the luminal domain of IRE1β showed anti-aggregation activity in vitro, and IRE1β was coprecipitated with the model unfolded proteins in cells. Strikingly, association with BiP was drastically reduced in IRE1β, while IRE1α was associated with BiP and dissociated upon ER stress. This is the first report indicating that, differently from IRE1α, the luminal event mediated by IRE1β involves direct interaction with unfolded proteins rather than association/dissociation with BiP, implying an intrinsic diversity in the sensing mechanism of mammalian sensors.Daisuke OikawaAkira KitamuraMasataka KinjoTakao IwawakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51290 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daisuke Oikawa Akira Kitamura Masataka Kinjo Takao Iwawaki Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
description	IRE1, an ER-localized transmembrane protein, plays a central role in the unfolded protein response (UPR). IRE1 senses the accumulation of unfolded proteins in its luminal domain and transmits a signal to the cytosolic side through its kinase and RNase domains. Although the downstream pathways mediated by two mammalian IRE1s, IRE1α and IRE1β, are well documented, their luminal events have not been fully elucidated. In particular, there have been no reports on how IRE1β senses the unfolded proteins. In this study, we performed a comparative analysis to clarify the luminal event mediated by the mammalian IRE1s. Confocal fluorescent microscopy using GFP-fused IRE1s revealed that IRE1β clustered into discrete foci upon ER stress. Also, fluorescence correlation spectroscopy (FCS) analysis in living cells indicated that the size of the IRE1β complex is robustly increased upon ER stress. Moreover, unlike IRE1α, the luminal domain of IRE1β showed anti-aggregation activity in vitro, and IRE1β was coprecipitated with the model unfolded proteins in cells. Strikingly, association with BiP was drastically reduced in IRE1β, while IRE1α was associated with BiP and dissociated upon ER stress. This is the first report indicating that, differently from IRE1α, the luminal event mediated by IRE1β involves direct interaction with unfolded proteins rather than association/dissociation with BiP, implying an intrinsic diversity in the sensing mechanism of mammalian sensors.
format	article
author	Daisuke Oikawa Akira Kitamura Masataka Kinjo Takao Iwawaki
author_facet	Daisuke Oikawa Akira Kitamura Masataka Kinjo Takao Iwawaki
author_sort	Daisuke Oikawa
title	Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
title_short	Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
title_full	Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
title_fullStr	Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
title_full_unstemmed	Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.
title_sort	direct association of unfolded proteins with mammalian er stress sensor, ire1β.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/8657280c05bf4234a941f93245d332ba
work_keys_str_mv	AT daisukeoikawa directassociationofunfoldedproteinswithmammalianerstresssensorire1b AT akirakitamura directassociationofunfoldedproteinswithmammalianerstresssensorire1b AT masatakakinjo directassociationofunfoldedproteinswithmammalianerstresssensorire1b AT takaoiwawaki directassociationofunfoldedproteinswithmammalianerstresssensorire1b
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Direct association of unfolded proteins with mammalian ER stress sensor, IRE1β.

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