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内质网蛋白在神经元中的转基因表达易于引发内质网应激。

Transgenic expression of endoplasmic reticulum proteins in neurons is prone to causing ER stress.

作者信息

Park Junhyun, Yogev Shaul

机构信息

Neuroscience, Yale University, New Haven, Connecticut, United States.

出版信息

MicroPubl Biol. 2025 May 29;2025. doi: 10.17912/micropub.biology.001547. eCollection 2025.

DOI:10.17912/micropub.biology.001547
PMID:40519643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12163624/
Abstract

In studying the endomembrane system, organelle-specific markers tagged with fluorescent proteins are used to visualize individual organelles. However, whether the expression of organelle marker perturbs the organelle's biology is not always apparent. We report that expression of a GFP-tagged Endoplasmic Reticulum (ER) protein causes low levels of ER stress that are challenging to detect in control animals. This stress is revealed only once the ER-associated degradation (ERAD) pathway is compromised. Our results highlight the vulnerability of the ER and suggest that the possible contribution of ER stress to phenotypes obtained with transgenic markers should be considered when interpreting the phenotypes.

摘要

在研究内膜系统时,带有荧光蛋白标签的细胞器特异性标记物被用于可视化单个细胞器。然而,细胞器标记物的表达是否会干扰细胞器的生物学功能并不总是显而易见的。我们报告称,一种绿色荧光蛋白(GFP)标记的内质网(ER)蛋白的表达会导致低水平的内质网应激,而在对照动物中很难检测到这种应激。只有当内质网相关降解(ERAD)途径受损时,这种应激才会显现出来。我们的结果突出了内质网的脆弱性,并表明在解释表型时,应考虑内质网应激对通过转基因标记物获得的表型可能产生的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f024/12163624/12721074dd7d/25789430-2025-micropub.biology.001547.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f024/12163624/12721074dd7d/25789430-2025-micropub.biology.001547.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f024/12163624/12721074dd7d/25789430-2025-micropub.biology.001547.jpg

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本文引用的文献

1
Quantitative measurement of cell-surface displayed proteins based on split-GFP assembly.基于 GFP 分裂组装的细胞表面展示蛋白的定量测量。
Microb Cell Fact. 2024 Apr 12;23(1):108. doi: 10.1186/s12934-024-02386-1.
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End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles.末端结合蛋白 1 在致密核心囊泡向轴突运输之前促进细胞体中特定的运动货物的结合。
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Neurexin and frizzled intercept axonal transport at microtubule minus ends to control synapse formation.
神经连接蛋白和卷曲受体在微管负端阻断轴突运输,从而控制突触形成。
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Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD).保守的细胞质结构域促进 Hrd1 泛素连接酶复合物形成,用于内质网相关降解(ERAD)。
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Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons.无脊椎动物神经元中粗面内质网膜蛋白和核糖体的靶向作用。
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