Related Experiment Video
Updated: Jun 12, 2025
14:29
Rapid In Vivo Fixation and Isolation of Translational Complexes from Eukaryotic Cells
Published on: December 25, 2021
3.9K
eIF2B localization and its regulation during the integrated stress response is cell-type specific
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
Summary
Cellular stress activates the integrated stress response (ISR), impacting translation via eukaryotic initiation factor 2B (eIF2B). This study reveals distinct eIF2B body patterns in neural cells during ISR, influencing cell-type specific responses to chronic stress.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Eukaryotic initiation factor 2B (eIF2B) regulates translation initiation and is inhibited by the integrated stress response (ISR) during cellular stress.
- Chronic ISR activation has pathological outcomes, as seen in Vanishing White Matter Disease (VWMD), which involves mutations in eIF2B affecting glial cells.
- eIF2B localization into eIF2B bodies is implicated in ISR regulation.
Purpose of the Study:
- To investigate the distinct patterns of eIF2B bodies in neuronal and glial cells under acute and chronic ISR activation.
- To determine if neural and glial cell types exhibit cell-type specific differences in response to chronic ISR induction.
Main Methods:
- Analysis of eIF2B body patterns in neuronal and glial cells under varying ISR conditions.
- Comparison of cellular responses to acute and chronic ISR induction across different neural cell types.
Main Results:
- Neuronal and glial cells display distinct eIF2B body patterns that correlate with acute and chronic ISR activation.
- While acute ISR induction elicits similar responses in neural and glial cells, chronic ISR leads to cell-type specific differences.
- These findings highlight the role of eIF2B localization in cellular stress adaptation.
Conclusions:
- Cellular stress and ISR activation induce distinct eIF2B localization patterns in neural and glial cells.
- Chronic ISR differentially affects neural and glial cell types, impacting their adaptation to stress.
- Understanding these cell-type specific responses provides crucial insights into neural adaptation to cellular stress and related disorders.
Related Concept Videos
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