在综合应激反应期间,eIF2B局部化及其调节是细胞类型特异性的
Filipe M Hanson1, Madalena I Ribeiro de Oliveira1, Alison K Cross1
1Biomolecular Sciences Research Centre, Industry and Innovation Research Institute (IRI), Sheffield Hallam University, Sheffield S1 1WB, UK.
iScience
|September 23, 2024
概括
细胞压力激活了综合应激反应 (ISR),通过真核生物启动因子2B (eIF2B) 影响翻译. 这项研究揭示了在ISR期间神经细胞中明显的eIF2B身体模式,影响细胞类型对慢性压力的特定反应.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 细胞启动因子2B (eIF2B) 调节翻译启动,并在细胞应激过程中被综合应激反应 (ISR) 抑制.
- 慢性ISR激活具有病理结果,如消失白质病 (VWMD) 中所见,这涉及eIF2B影响质细胞的突变.
- 在ISR监管中涉及到eIF2B体中的eIF2B本地化.
研究的目的:
- 在急性和慢性ISR激活下,研究神经元和质细胞中eIF2B体的独特模式.
- 为了确定神经和质细胞类型是否在对慢性ISR诱导的反应中表现出细胞类型特定的差异.
主要方法:
- 在不同ISR条件下分析神经元和质细胞中的eIF2B体型.
- 通过不同神经细胞类型对急性和慢性ISR诱导进行细胞反应的比较.
主要成果:
- 神经和质细胞表现出明显的eIF2B身体模式,与急性和慢性ISR激活相关.
- 虽然急性ISR诱导在神经和质细胞中引起了类似的反应,但慢性ISR导致了细胞类型的特异性差异.
- 这些发现突显了eIF2B局部化在细胞应激适应中的作用.
结论:
- 细胞应激和ISR激活会在神经和质细胞中诱导不同的eIF2B局部化模式.
- 慢性ISR不同影响神经和质细胞类型,影响它们对压力的适应.
- 了解这些细胞类型特异性反应为神经适应细胞压力和相关疾病提供了关键的见解.
相关概念视频
01:31Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
01:23Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
01:37The Unfolded Protein Response
4.5K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
01:45Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
02:24Regulation of Expression Occurs at Multiple Steps
22.5K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.5K
02:22Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K