Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins

被引:242
作者
Kimata, Yukio [1 ]
Ishiwata-Kimata, Yuki
Ito, Tatsuhiko
Hirata, Aiko
Suzuki, Tomohide
Oikawa, Daisuke
Takeuchi, Masato
Kohno, Kenji
机构
[1] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 630, Japan
[2] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrat Biosci, Kashiwa, Chiba 2778562, Japan
关键词
D O I
10.1083/jcb.200704166
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chaperone protein BiP binds to Ire1 and dissociates in response to endoplasmic reticulum ( ER) stress. However, it remains unclear how the signal transducer Ire1 senses ER stress and is subsequently activated. The crystal structure of the core stress-sensing region (CSSR) of yeast Ire1 luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins. We demonstrate that, upon ER stress, Ire1 clusters and actually interacts with unfolded proteins. Ire1 mutations that affect these phenomena reveal that Ire1 is activated via two steps, both of which are ER stress regulated, albeit in different ways. In the first step, BiP dissociation from Ire1 leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules.
引用
收藏
页码:75 / 86
页数:12
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