1. eIF2B localization and its regulation during the integrated stress response is cell-type specific.
- Author
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Hanson FM, Ribeiro de Oliveira MI, Cross AK, Allen KE, and Campbell SG
- Abstract
Eukaryotic initiation factor 2B (eIF2B) controls translation initiation by recycling inactive eIF2-GDP to active eIF2-GTP. Under cellular stress, the integrated stress response (ISR) is activated inhibiting eIF2B activity resulting in the translation attenuation and reprogramming of gene expression to overcome the stress. The ISR can dictate cell fate wherein chronic activation has pathological outcomes. Vanishing white matter disease (VWMD) is a chronic ISR-related disorder with mutations in eIF2B targeting astrocyte and oligodendrocyte cells. Regulation of eIF2B localization (eIF2B bodies) has been implicated in the ISR. We present evidence that neuronal and glial cell types possess distinct patterns of eIF2B bodies which change in a manner correlating to acute and chronic ISR activation. We also demonstrate that while neural and glial cell types respond similarly to the acute induction of the ISR a chronic ISR exerts cell-type specific differences. These findings provide key insights into neural cell responses and adaptation to cellular stress., Competing Interests: For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted article version of this article arising from this submission. The authors have no relevant financial or non-financial interests to disclose. The author Dr Filipe Hanson completed this work as part of his PhD studies at Sheffield Hallam University. He now works as a Research Scientist for UCB Pharma, Slough, UK. The author Dr Madalena deOliveira contributed to this work as part of her PhD studies at Sheffield Hallam University. She now works as a Postdoctoral Fellow for MSD, UK., (© 2024 The Author(s).)
- Published
- 2024
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