Limits...
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

Phase I and phase II cells activate the ERSU pathway.(A) Percentage of phase I (purple) and phase II (gray) cells that showed one bud or two buds after Tm treatment. Error bars indicate SD from three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.06970.012
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555637&req=5

fig5s1: Phase I and phase II cells activate the ERSU pathway.(A) Percentage of phase I (purple) and phase II (gray) cells that showed one bud or two buds after Tm treatment. Error bars indicate SD from three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.06970.012

Mentions: We found that phase I cells exhibited a cytokinesis block and did not undergo cell division at 80 min after α-factor release (1 hr after Tm addition; Figure 5A,C and Figure 5—figure supplement 2). Even at 200 min after release (3 hr post-Tm), >85% of phase I cells remained undivided (Figure 5A,C; purple bars and Figure 5—figure supplement 2). Furthermore, in most phase I cells, the cER remained in the mother cell (Figure 5D–E and Figure 5—figure supplement 4). In contrast, at 50 min after α-factor release (before induction of ER stress), almost all of the phase II daughter cells had already inherited the cER (Figure 5D,F and Figure 5—figure supplement 5). After Tm addition, these cells underwent cytokinesis (cell division), and at 1 hr after Tm addition (110 min), ∼50% of cells were derived from TR-positive mother cells, and the remaining ∼50% were TR-negative and were derived from the first daughter cell that emerged after α-factor release (Figure 5B,C, 110 min gray bars and Figure 5—figure supplement 3). After division, the number of cells with the cER in the daughter cell was small (Figure 5D,F; 110 min, and Figure 5—figure supplement 5). The observed differences between phase I and phase II cells in cytokinesis and ER inheritance were not due to an inability of phase II cells to respond to Tm. Phase I and II cells showed similar degrees of UPR activation after ER stress, as reflected in the levels of spliced HAC1 mRNA resulting from activated Ire1 RNase-mediated mRNA cleavage (Figure 5G,H). Intriguingly, phase II cells exhibited a block in both cytokinesis and cER inheritance block at the second round of division, and the daughter cell arising from the first cell division did not further divide. Instead, we observed cells with two daughter cells. This was also observed for phase I cells in which the second daughter cell started to emerge after 3 hr of Tm treatment. At this point (Tm, 3 hr), ∼13% of phase II and ∼20% of phase I cells had two buds (Figure 5—figure supplement 1). These results therefore demonstrate that cells in which the cER is already in the daughter cell at the time of ER stress induction proceed through cytokinesis once, but display blocks in both cytokinesis and cER inheritance in the next cell cycle.


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

Piña FJ, Niwa M - Elife (2015)

Phase I and phase II cells activate the ERSU pathway.(A) Percentage of phase I (purple) and phase II (gray) cells that showed one bud or two buds after Tm treatment. Error bars indicate SD from three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.06970.012
© Copyright Policy
Related In: Results  -  Collection

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

fig5s1: Phase I and phase II cells activate the ERSU pathway.(A) Percentage of phase I (purple) and phase II (gray) cells that showed one bud or two buds after Tm treatment. Error bars indicate SD from three independent experiments.DOI:http://dx.doi.org/10.7554/eLife.06970.012
Mentions: We found that phase I cells exhibited a cytokinesis block and did not undergo cell division at 80 min after α-factor release (1 hr after Tm addition; Figure 5A,C and Figure 5—figure supplement 2). Even at 200 min after release (3 hr post-Tm), >85% of phase I cells remained undivided (Figure 5A,C; purple bars and Figure 5—figure supplement 2). Furthermore, in most phase I cells, the cER remained in the mother cell (Figure 5D–E and Figure 5—figure supplement 4). In contrast, at 50 min after α-factor release (before induction of ER stress), almost all of the phase II daughter cells had already inherited the cER (Figure 5D,F and Figure 5—figure supplement 5). After Tm addition, these cells underwent cytokinesis (cell division), and at 1 hr after Tm addition (110 min), ∼50% of cells were derived from TR-positive mother cells, and the remaining ∼50% were TR-negative and were derived from the first daughter cell that emerged after α-factor release (Figure 5B,C, 110 min gray bars and Figure 5—figure supplement 3). After division, the number of cells with the cER in the daughter cell was small (Figure 5D,F; 110 min, and Figure 5—figure supplement 5). The observed differences between phase I and phase II cells in cytokinesis and ER inheritance were not due to an inability of phase II cells to respond to Tm. Phase I and II cells showed similar degrees of UPR activation after ER stress, as reflected in the levels of spliced HAC1 mRNA resulting from activated Ire1 RNase-mediated mRNA cleavage (Figure 5G,H). Intriguingly, phase II cells exhibited a block in both cytokinesis and cER inheritance block at the second round of division, and the daughter cell arising from the first cell division did not further divide. Instead, we observed cells with two daughter cells. This was also observed for phase I cells in which the second daughter cell started to emerge after 3 hr of Tm treatment. At this point (Tm, 3 hr), ∼13% of phase II and ∼20% of phase I cells had two buds (Figure 5—figure supplement 1). These results therefore demonstrate that cells in which the cER is already in the daughter cell at the time of ER stress induction proceed through cytokinesis once, but display blocks in both cytokinesis and cER inheritance in the next cell cycle.

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