Watching how cells deal with stress
Inositol-required enzyme 1 alpha (IRE1α)-dependent processing and endoplasmic reticulum (ER) association of XBP1u transcripts during stress. (A) Reporter construct design: non-splicable (dark blue) and spliced (light blue) reporter transcripts are identical to XBP1 wild-type (WT; red) except for point mutations in the intron (non-splicable) or complete lack thereof (spliced). (B) Representative live cell images of XBP1 splice site mutant reporters (blue) in HeLa cells expressing NLS-stdMCP-stdHalo and Sec61b-SNAP as ER marker (grey). (C) Box plot showing ER association quantification from correlated diffusion and ER colocalization analysis for XBP1 WT (red), unspliceable (dark blue), and spliced (light blue) reporter transcripts. Different opacities represent experimental conditions: no treatment (Ctrl), ER stress induced with 3-4 hours 5 µg/ml tunicamycin (TM), ER stress induced with 3-4 hours 5 µg/ml TM under IRE1α inhibition with 4µ8C (TM + 4µ8C). Statistical test: unpaired t-test, p-values: (p≥0.05)=ns; (peLife (2022). DOI: 10.7554/eLife.75580
eLife (2022). DOI: 10.7554/eLife.75580″ width=”617″ height=”530″/>
FMI researchers developed an imaging approach that allowed them to visualize individual molecules involved in the cell’s response to stress.
When a cell is exposed to stressors such as toxins, it switches on pathways aimed at repairing damage.
One of these pathways is called the “unfolded protein response,” which detects unfolded or misfolded proteins in the endoplasmic reticulum — a cell organelle designated for folding proteins destined for other organelles or secreted by the cell.
The unfolded protein response is dependent on the enzyme IRE1a, which binds transcripts of the gene XBP1 and modifies them on the surface of the endoplasmic reticulum. Once modified, XBP1 transcripts are translated into proteins that travel to the nucleus and turn on genes involved in aiding protein folding and quality control.
Scientists led by Franka Voigt, a researcher in the Chao group at the FMI, developed an imaging approach that allowed them to take snapshots of individual XBP1 transcripts on the surface of the endoplasmic reticulum. This approach enabled the researchers to investigate how XBP1 transcripts are recruited and modified by IRE1a.
The findings, published in eLifewill help to better understand how cells respond to stress.
Silvia Gómez-Puerta et al, Live imaging of the co-translational recruitment of XBP1 mRNA to the ER and its processing by diffuse, unpolarized IRE1α, eLife (2022). DOI: 10.7554/eLife.75580
Quote: Video: Watching Cells Cope With Stress (2022, June 29) Retrieved June 29, 2022 from https://phys.org/news/2022-06-video-cells-stress.html
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