亚砷酸钠通过促进 PICK1 BAR 结构域同源二聚体的形成来诱导凝集体的形成。

IF 3.1 3区 生物学 Q3 CELL BIOLOGY
Molecular Biology of the Cell Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI:10.1091/mbc.E24-05-0201
John Ho Chun Lai, Marianthi Tsogka, Jun Xia
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引用次数: 0

摘要

凝集体(aggresome)是一种核周结构,能封存折叠错误的蛋白质。它与多种神经退行性疾病有关。研究发现,富含 PICK1 的核周结构可被细胞应激物诱导,并与微管组织中心(MTOC)标记物和泛素共定位,因此被归类为侵袭体。研究发现,亚砷酸钠(而非砷酸盐)能通过综合应激反应(ISR)独立途径有效诱导侵染体的形成。在HEK293T细胞中,在亚砷酸盐胁迫下,PICK1优先定位到侵染体,并有利于PICK1同源二聚体的形成。此外,PICK1 还能促进蛋白质进入侵染体。这项研究表明,亚砷酸盐可同时诱导 RNA 应激颗粒和侵染体的形成,而 PICK1 则显示出有条件地定位到侵染体,这表明 PICK1 可能参与了神经退行性疾病的研究。[媒体:见正文] [媒体:见正文]。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation.

The aggresome is a perinuclear structure that sequesters misfolded proteins. It is implicated in various neurodegenerative diseases. The perinuclear structure enriched with protein interacting with C kinase 1 (PICK1) was found to be inducible by cellular stressors, colocalizing with microtubule-organizing center markers and ubiquitin, hence classifying it as an aggresome. Sodium arsenite but not arsenate was found to potently induce aggresome formation through an integrated stress response-independent pathway. In HEK293T cells, under arsenite stress, PICK1 localization to the aggresome was prioritized, and formation of PICK1 homodimers was favored. Additionally, PICK1 could enhance protein entry into aggresomes. This study shows that arsenite can induce the formation of both RNA stress granules and aggresomes at the same time, and that PICK1 shows conditional localization to aggresomes, suggesting a possible involvement of PICK1 in neurodegenerative diseases.

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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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