Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP

Summary: The endoplasmic reticulum (ER) stress response controls the balance between cellular survival and death. Here, we implicate SCOTIN, an interferon-inducible ER protein, in activating the ER stress response and modulating cell fate through its proline-rich domain (PRD)-mediated cytosolic cond...

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Main Authors: Areum Jo, Minkyo Jung, Ji Young Mun, Young Jin Kim, Joo-Yeon Yoo
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725000683
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author Areum Jo
Minkyo Jung
Ji Young Mun
Young Jin Kim
Joo-Yeon Yoo
author_facet Areum Jo
Minkyo Jung
Ji Young Mun
Young Jin Kim
Joo-Yeon Yoo
author_sort Areum Jo
collection DOAJ
description Summary: The endoplasmic reticulum (ER) stress response controls the balance between cellular survival and death. Here, we implicate SCOTIN, an interferon-inducible ER protein, in activating the ER stress response and modulating cell fate through its proline-rich domain (PRD)-mediated cytosolic condensation. SCOTIN overexpression leads to the formation of condensates enveloping multiple layers of the ER, accompanied by morphological signs of organelle stress. Luminal BiP chaperone proteins are sequestered within these SCOTIN condensates, which elicit ER stress responses. The colocalization of luminal BiP with SCOTIN is strictly contingent upon the PRD-mediated condensation of SCOTIN in the cytosolic compartment, closely associated with the ER membrane. The cysteine-rich domain (CRD) of SCOTIN, along with the condensation-prone PRD domain, is required for ER stress induction. We propose that membrane-associated condensation transduces signals across the ER membrane, leading to the induction of BiP assembly and the ER stress response.
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issn 2211-1247
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publishDate 2025-02-01
publisher Elsevier
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series Cell Reports
spelling doaj-art-2cda68f2f0a541988a53a63f832a42b02025-08-20T03:11:33ZengElsevierCell Reports2211-12472025-02-0144211529710.1016/j.celrep.2025.115297Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiPAreum Jo0Minkyo Jung1Ji Young Mun2Young Jin Kim3Joo-Yeon Yoo4Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of KoreaNeural Circuit Research Group, Korea Brain Research Institute, Daegu 41062, Republic of KoreaNeural Circuit Research Group, Korea Brain Research Institute, Daegu 41062, Republic of KoreaDepartment of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of KoreaDepartment of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea; Corresponding authorSummary: The endoplasmic reticulum (ER) stress response controls the balance between cellular survival and death. Here, we implicate SCOTIN, an interferon-inducible ER protein, in activating the ER stress response and modulating cell fate through its proline-rich domain (PRD)-mediated cytosolic condensation. SCOTIN overexpression leads to the formation of condensates enveloping multiple layers of the ER, accompanied by morphological signs of organelle stress. Luminal BiP chaperone proteins are sequestered within these SCOTIN condensates, which elicit ER stress responses. The colocalization of luminal BiP with SCOTIN is strictly contingent upon the PRD-mediated condensation of SCOTIN in the cytosolic compartment, closely associated with the ER membrane. The cysteine-rich domain (CRD) of SCOTIN, along with the condensation-prone PRD domain, is required for ER stress induction. We propose that membrane-associated condensation transduces signals across the ER membrane, leading to the induction of BiP assembly and the ER stress response.http://www.sciencedirect.com/science/article/pii/S2211124725000683CP: Cell biology
spellingShingle Areum Jo
Minkyo Jung
Ji Young Mun
Young Jin Kim
Joo-Yeon Yoo
Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
Cell Reports
CP: Cell biology
title Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
title_full Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
title_fullStr Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
title_full_unstemmed Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
title_short Membrane-tethered SCOTIN condensates elicit an endoplasmic reticulum stress response by sequestering luminal BiP
title_sort membrane tethered scotin condensates elicit an endoplasmic reticulum stress response by sequestering luminal bip
topic CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124725000683
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