Characterization of Stress Granule Protein Turnover in Neuronal Progenitor Cells Using Correlative STED and NanoSIMS Imaging

Rabasco, StefaniaGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology (författare)

Stress granules (SGs) are stress-induced biomolecular condensates which originate primarily from inactivated RNA translation machinery and translation initiation factors. SG formation is an important defensive mechanism for cell survival, while its dysfunction has been linked to neurodegenerative diseases. However, the molecular mechanisms of SG assembly and disassembly, as well as their impacts on cellular recovery, are not fully understood. More thorough investigations into the molecular dynamics of SG pathways are required to understand the pathophysiological roles of SGs in cellular systems. Here, we characterize the SG and cytoplasmic protein turnover in neuronal progenitor cells (NPCs) under stressed and non-stressed conditions using correlative STED and NanoSIMS imaging. We incubate NPCs with isotopically labelled (15N) leucine and stress them with the ER stressor thapsigargin (TG). A correlation of STED and NanoSIMS allows the localization of individual SGs (using STED), and their protein turnover can then be extracted based on the 15N/14N ratio (using NanoSIMS). We found that TG-induced SGs, which are highly dynamic domains, recruit their constituents predominantly from the cytoplasm. Moreover, ER stress impairs the total cellular protein turnover regimen, and this impairment is not restored after the commonly proceeded stress recovery period.

Lork, AliciaGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xloral (författare)
Berlin, EmmanuelGothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xberll (författare)
Nguyen, Tho D. K.Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xngduc (författare)
Ernst, Carl (författare)
Locker, Nicolas (författare)
Ewing, Andrew G,1957Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xewian (författare)
Phan, Nhu TN,1981Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology(Swepub:gu)xphant (författare)
Göteborgs universitetInstitutionen för kemi och molekylärbiologi (creator_code:org_t)

Ingår i:International Journal of Molecular Sciences: MDPI AG241661-65961422-0067

Av författaren/redakt...: Rabasco, Stefani ...; Lork, Alicia; Berlin, Emmanuel; Nguyen, Tho D. K ...; Ernst, Carl; Locker, Nicolas; visa fler...; Ewing, Andrew G, ...; Phan, Nhu TN, 19 ...; visa färre...

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