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

Many species of yeast form new cells by a process known as budding in which a small daughter cell ‘buds’ out of a larger mother cell. Mothers can only produce a limited number of buds before they die of old age. However, age is reset in the daughters to ensure that they are fully rejuvenated when born. Therefore, the mother cell needs to prevent the factors that cause aging and cell damage from entering the daughter. Inside cells, proteins are made and folded correctly in a structure called the endoplasmic reticulum. If proteins are not folded properly, they are normally rapidly destroyed. However, if a cell requires lots of proteins to be made quickly, this can sometimes overwhelm and ‘stress’ the endoplasmic reticulum. When this occurs, proteins start misfolding and clump up to form toxic aggregates, some of which collect inside the endoplasmic reticulum. The Endoplasmic Reticulum Stress Surveillance (ERSU) pathway monitors the health of the endoplasmic reticulum and prevents ‘stressed’ endoplasmic reticulum from entering daughter cells, which can cause them to die. By visualizing the endoplasmic reticulum and the aggregates contained within it during budding in the yeast species Saccharomyces cerevisiae, Pina and Niwa have now found that the ERSU pathway can also prevent these aggregates from entering daughter cells. However, if the ERSU pathway is not switched on—as may be the case if the level of endoplasmic reticulum stress is very low—then aggregates can enter the daughter cells. This is in contrast to protein aggregates that form elsewhere in the cell, which are normally always kept inside the mother cell due to their damaging effects. These results suggest that the ERSU pathway is responsible for preventing protein aggregates in the endoplasmic reticulum from entering daughter cells, but only does so when these aggregates stress the endoplasmic reticulum. Future research will aim to identify how the ERSU pathway senses protein aggregates and prevents the transmission of damaged endoplasmic reticulum.