Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering

Paulina Kettel; Laura Marosits; Elena Spinetti; Michael Rechberger; Caterina Giannini; Philipp Radler; Isabell Niedermoser; Irmgard Fischer; Gijs A. Versteeg; Martin Loose; Roberto Covino; G. Elif Karagöz

doi:10.1038/s44318-024-00207-0

Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering

Paulina Kettel, Laura Marosits, Elena Spinetti, Michael Rechberger, Caterina Giannini, Philipp Radler, Isabell Niedermoser, Irmgard Fischer, Gijs A. Versteeg, Martin Loose, Roberto Covino, G. Elif Karagöz (Corresponding author)

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

(Figure presented.) Proteotoxic stress causes the endoplasmic reticulum (ER) stress sensor IRE1α to cluster, but the mechanistic basis of its cluster formation remains poorly understood. This study reveals that disordered regions within the protein’s ER lumenal domain (LD) mediate its assembly into signaling clusters. IRE1α LD forms biomolecular condensates in solution. Disordered regions within IRE1α LD drive the formation of condensates through weak multivalent interactions. Binding of unfolded polypeptide ligands and membrane-tethering leads to the formation of stable IRE1α LD clusters. The integrity of the disordered regions in its lumenal domain is critical for IRE1α clustering and unfolded protein response (UPR) signaling in cells.

Original language	English
Pages (from-to)	4668-4698
Number of pages	31
Journal	EMBO Journal
Volume	43
Issue number	20
DOIs	https://doi.org/10.1038/s44318-024-00207-0
Publication status	Published - 15 Oct 2024

Austrian Fields of Science 2012

106023 Molecular biology

Keywords

Biomolecular Condensates
IRE1
Supported Lipid Bilayers
Unfolded Protein Response

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10.1038/s44318-024-00207-0

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title = "Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering",

abstract = "(Figure presented.) Proteotoxic stress causes the endoplasmic reticulum (ER) stress sensor IRE1α to cluster, but the mechanistic basis of its cluster formation remains poorly understood. This study reveals that disordered regions within the protein{\textquoteright}s ER lumenal domain (LD) mediate its assembly into signaling clusters. IRE1α LD forms biomolecular condensates in solution. Disordered regions within IRE1α LD drive the formation of condensates through weak multivalent interactions. Binding of unfolded polypeptide ligands and membrane-tethering leads to the formation of stable IRE1α LD clusters. The integrity of the disordered regions in its lumenal domain is critical for IRE1α clustering and unfolded protein response (UPR) signaling in cells.",

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doi = "10.1038/s44318-024-00207-0",

language = "English",

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T1 - Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering

AU - Kettel, Paulina

AU - Marosits, Laura

AU - Spinetti, Elena

AU - Rechberger, Michael

AU - Giannini, Caterina

AU - Radler, Philipp

AU - Niedermoser, Isabell

AU - Fischer, Irmgard

AU - Versteeg, Gijs A.

AU - Loose, Martin

AU - Covino, Roberto

AU - Karagöz, G. Elif

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/10/15

Y1 - 2024/10/15

N2 - (Figure presented.) Proteotoxic stress causes the endoplasmic reticulum (ER) stress sensor IRE1α to cluster, but the mechanistic basis of its cluster formation remains poorly understood. This study reveals that disordered regions within the protein’s ER lumenal domain (LD) mediate its assembly into signaling clusters. IRE1α LD forms biomolecular condensates in solution. Disordered regions within IRE1α LD drive the formation of condensates through weak multivalent interactions. Binding of unfolded polypeptide ligands and membrane-tethering leads to the formation of stable IRE1α LD clusters. The integrity of the disordered regions in its lumenal domain is critical for IRE1α clustering and unfolded protein response (UPR) signaling in cells.

AB - (Figure presented.) Proteotoxic stress causes the endoplasmic reticulum (ER) stress sensor IRE1α to cluster, but the mechanistic basis of its cluster formation remains poorly understood. This study reveals that disordered regions within the protein’s ER lumenal domain (LD) mediate its assembly into signaling clusters. IRE1α LD forms biomolecular condensates in solution. Disordered regions within IRE1α LD drive the formation of condensates through weak multivalent interactions. Binding of unfolded polypeptide ligands and membrane-tethering leads to the formation of stable IRE1α LD clusters. The integrity of the disordered regions in its lumenal domain is critical for IRE1α clustering and unfolded protein response (UPR) signaling in cells.

KW - Biomolecular Condensates

KW - IRE1

KW - Supported Lipid Bilayers

KW - Unfolded Protein Response

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DO - 10.1038/s44318-024-00207-0

M3 - Article

C2 - 39232130

AN - SCOPUS:85203078172

SN - 0261-4189

VL - 43

SP - 4668

EP - 4698

JO - EMBO Journal

JF - EMBO Journal

IS - 20

ER -

Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering

Abstract

Austrian Fields of Science 2012

Keywords

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