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聚集体形成过程中两种错误折叠蛋白的空间差异表征

Characterization of Spatial Differences in Two Misfolded Proteins During Aggresome Formation.

作者信息

Goldy Jordan N, Youker Robert T

机构信息

Department of Biology, Emory University, Atlanta, Georgia, United States.

Department of Biology , Western Carolina University, Cullowhee, North Carolina, United States.

出版信息

MicroPubl Biol. 2024 Oct 21;2024. doi: 10.17912/micropub.biology.001312. eCollection 2024.

DOI:10.17912/micropub.biology.001312
PMID:39502423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536049/
Abstract

Cells have evolved an elaborate network of folding and degradation pathways to maintain the native state of proteins. If these pathways are disrupted (e.g., mutation) or their capacity is exceeded then protein aggregates form in cells. Cells sequester these aggregated proteins into aggresome or aggresome-like bodies as a protective mechanism. In this study, we co-expressed two model misfolded proteins in HEK293 cells and measured aggresome formation upon proteasomal inhibition. We observed spatial differences in early time points of aggresome formation upon co-expression of the misfolded proteins compared to individual expression in cells.

摘要

细胞已经进化出一套复杂的折叠和降解途径网络,以维持蛋白质的天然状态。如果这些途径被破坏(例如,发生突变)或超出其能力范围,那么细胞内就会形成蛋白质聚集体。细胞将这些聚集的蛋白质隔离到聚集体或类聚集体中,作为一种保护机制。在本研究中,我们在人胚肾293细胞中共表达了两种模型错误折叠蛋白,并在蛋白酶体抑制后测量聚集体的形成。我们观察到,与细胞中单独表达相比,共表达错误折叠蛋白时,聚集体形成的早期时间点存在空间差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f154/11536049/5039fcd1da02/25789430-2024-micropub.biology.001312.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f154/11536049/5039fcd1da02/25789430-2024-micropub.biology.001312.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f154/11536049/5039fcd1da02/25789430-2024-micropub.biology.001312.jpg

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本文引用的文献

1
Alternative systems for misfolded protein clearance: life beyond the proteasome.错误折叠蛋白清除的替代系统:蛋白酶体之外的生命。
FEBS J. 2021 Aug;288(15):4464-4487. doi: 10.1111/febs.15617. Epub 2020 Nov 20.
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Mechanisms, regulation and functions of the unfolded protein response.未折叠蛋白反应的机制、调控和功能。
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Cell-Nonautonomous Regulation of Proteostasis in Aging and Disease.细胞非自主调控衰老和疾病中的蛋白质稳态。
Cold Spring Harb Perspect Biol. 2020 Apr 1;12(4):a034074. doi: 10.1101/cshperspect.a034074.
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The Ubiquitin System, Autophagy, and Regulated Protein Degradation.泛素系统、自噬和调控蛋白降解。
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Proteasomal and Autophagic Degradation Systems.蛋白酶体和自噬降解系统。
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Spatially organized aggregation of misfolded proteins as cellular stress defense strategy.错误折叠蛋白质的空间组织聚集作为细胞应激防御策略。
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Confinement to organelle-associated inclusion structures mediates asymmetric inheritance of aggregated protein in budding yeast.隔离到细胞器相关的包含结构中介导了出芽酵母中聚集蛋白的不对称遗传。
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Compartmentalization of superoxide dismutase 1 (SOD1G93A) aggregates determines their toxicity.超氧化物歧化酶 1(SOD1G93A)聚集体的分隔决定了它们的毒性。
Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15811-6. doi: 10.1073/pnas.1205829109. Epub 2012 Sep 11.