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The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance.

Piña FJ, Niwa M - Elife (2015)

Bottom Line: Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases.By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER.Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Sciences, Section of Molecular Biology, Univeristy of California, San Diego, San Diego, United States.

ABSTRACT
Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases. Protein aggregates are also formed within the endoplasmic reticulum (ER), although the fate of ER protein aggregates, specifically during cell division, is not well understood. By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER. In contrast, under conditions of normal ER inheritance, ER protein aggregates can enter the daughter cell. Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.

No MeSH data available.


Related in: MedlinePlus

Inheritance of cER and CFTR aggregates at different stages of the cell cycle.(A) cER inheritance by different classes of WT GFP-CFTR-expressing cells treated without or with Tm (1 μg/ml, 2 hr). GFP-CFTR expression was induced by incubation in copper-containing medium (Cu). Graphs (B) and (C) are the same as those in Figure 2D,F but are shown again for comparison. (D) Percentage of daughter cells containing GFP-CFTR aggregates following incubation with or without Tm. (E and F) Percentage of daughter cells containing cER and GFP-CFTR aggregates (yellow), cER but no GFP-CFTR aggregates (gray), and neither cER nor GFP-CFTR aggregates (blue) for each class of cells. Cells were untreated (E) or treated with 1 μg/ml Tm (F). (E) The graph shown is the same as Figure 2H and is presented for comparison. (G and H) Distribution of GFP-CFTR aggregates per bud in all (Total), class I, and class II + III cells untreated (G) or treated with Tm (H).DOI:http://dx.doi.org/10.7554/eLife.06970.006
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fig2s2: Inheritance of cER and CFTR aggregates at different stages of the cell cycle.(A) cER inheritance by different classes of WT GFP-CFTR-expressing cells treated without or with Tm (1 μg/ml, 2 hr). GFP-CFTR expression was induced by incubation in copper-containing medium (Cu). Graphs (B) and (C) are the same as those in Figure 2D,F but are shown again for comparison. (D) Percentage of daughter cells containing GFP-CFTR aggregates following incubation with or without Tm. (E and F) Percentage of daughter cells containing cER and GFP-CFTR aggregates (yellow), cER but no GFP-CFTR aggregates (gray), and neither cER nor GFP-CFTR aggregates (blue) for each class of cells. Cells were untreated (E) or treated with 1 μg/ml Tm (F). (E) The graph shown is the same as Figure 2H and is presented for comparison. (G and H) Distribution of GFP-CFTR aggregates per bud in all (Total), class I, and class II + III cells untreated (G) or treated with Tm (H).DOI:http://dx.doi.org/10.7554/eLife.06970.006

Mentions: In contrast to the findings in CPY*-expressing cells, we found that cER inheritance was not affected by expression of GFP-CFTR (Figure 2D) unless the cells were also subjected to Tm treatment (Figure 2—figure supplement 2A–C). Therefore, CFTR aggregation presented an opportunity to evaluate the transmission of ER protein aggregates independently of the ER inheritance block. Quantitation of the number of CFTR aggregates and cER in the mother and daughter cells showed that virtually all class I, II, and III daughter cells contained CFTR aggregates (Figure 2H: yellow and Figure 2—figure supplement 2G), indicating no preferential retention of CFTR aggregates by the mother cells. Thus, although CPY* and CFTR both form ER protein aggregates in yeast cells, preferential retention of aggregates was only observed in the CPY*-expressing cells, which also displayed the cER inheritance block. Finally, the cER inheritance block and asymmetric distribution of CFTR aggregates was observed in GFP-CFTR-expressing cells after Tm treatment (Figure 2—figure supplement 2D–F,H), strengthening the relationship between ER inheritance and ER protein aggregate distribution.


The ER Stress Surveillance (ERSU) pathway regulates daughter cell ER protein aggregate inheritance.

Piña FJ, Niwa M - Elife (2015)

Inheritance of cER and CFTR aggregates at different stages of the cell cycle.(A) cER inheritance by different classes of WT GFP-CFTR-expressing cells treated without or with Tm (1 μg/ml, 2 hr). GFP-CFTR expression was induced by incubation in copper-containing medium (Cu). Graphs (B) and (C) are the same as those in Figure 2D,F but are shown again for comparison. (D) Percentage of daughter cells containing GFP-CFTR aggregates following incubation with or without Tm. (E and F) Percentage of daughter cells containing cER and GFP-CFTR aggregates (yellow), cER but no GFP-CFTR aggregates (gray), and neither cER nor GFP-CFTR aggregates (blue) for each class of cells. Cells were untreated (E) or treated with 1 μg/ml Tm (F). (E) The graph shown is the same as Figure 2H and is presented for comparison. (G and H) Distribution of GFP-CFTR aggregates per bud in all (Total), class I, and class II + III cells untreated (G) or treated with Tm (H).DOI:http://dx.doi.org/10.7554/eLife.06970.006
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555637&req=5

fig2s2: Inheritance of cER and CFTR aggregates at different stages of the cell cycle.(A) cER inheritance by different classes of WT GFP-CFTR-expressing cells treated without or with Tm (1 μg/ml, 2 hr). GFP-CFTR expression was induced by incubation in copper-containing medium (Cu). Graphs (B) and (C) are the same as those in Figure 2D,F but are shown again for comparison. (D) Percentage of daughter cells containing GFP-CFTR aggregates following incubation with or without Tm. (E and F) Percentage of daughter cells containing cER and GFP-CFTR aggregates (yellow), cER but no GFP-CFTR aggregates (gray), and neither cER nor GFP-CFTR aggregates (blue) for each class of cells. Cells were untreated (E) or treated with 1 μg/ml Tm (F). (E) The graph shown is the same as Figure 2H and is presented for comparison. (G and H) Distribution of GFP-CFTR aggregates per bud in all (Total), class I, and class II + III cells untreated (G) or treated with Tm (H).DOI:http://dx.doi.org/10.7554/eLife.06970.006
Mentions: In contrast to the findings in CPY*-expressing cells, we found that cER inheritance was not affected by expression of GFP-CFTR (Figure 2D) unless the cells were also subjected to Tm treatment (Figure 2—figure supplement 2A–C). Therefore, CFTR aggregation presented an opportunity to evaluate the transmission of ER protein aggregates independently of the ER inheritance block. Quantitation of the number of CFTR aggregates and cER in the mother and daughter cells showed that virtually all class I, II, and III daughter cells contained CFTR aggregates (Figure 2H: yellow and Figure 2—figure supplement 2G), indicating no preferential retention of CFTR aggregates by the mother cells. Thus, although CPY* and CFTR both form ER protein aggregates in yeast cells, preferential retention of aggregates was only observed in the CPY*-expressing cells, which also displayed the cER inheritance block. Finally, the cER inheritance block and asymmetric distribution of CFTR aggregates was observed in GFP-CFTR-expressing cells after Tm treatment (Figure 2—figure supplement 2D–F,H), strengthening the relationship between ER inheritance and ER protein aggregate distribution.

Bottom Line: Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases.By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER.Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Sciences, Section of Molecular Biology, Univeristy of California, San Diego, San Diego, United States.

ABSTRACT
Stress induced by cytoplasmic protein aggregates can have deleterious consequences for the cell, contributing to neurodegeneration and other diseases. Protein aggregates are also formed within the endoplasmic reticulum (ER), although the fate of ER protein aggregates, specifically during cell division, is not well understood. By simultaneous visualization of both the ER itself and ER protein aggregates, we found that ER protein aggregates that induce ER stress are retained in the mother cell by activation of the ER Stress Surveillance (ERSU) pathway, which prevents inheritance of stressed ER. In contrast, under conditions of normal ER inheritance, ER protein aggregates can enter the daughter cell. Thus, whereas cytoplasmic protein aggregates are retained in the mother cell to protect the functional capacity of daughter cells, the fate of ER protein aggregates is determined by whether or not they activate the ERSU pathway to impede transmission of the cortical ER during the cell cycle.

No MeSH data available.


Related in: MedlinePlus