The unfolded protein response (UPR) helps the endoplasmic reticulum (ER) to cope with stressful situations — such as elevated levels of unfolded proteins — by increasing the functional capacity of the ER. Bicknell et al. now show that the UPR not only functions under conditions of extreme cellular stress, but that it is also activated by normal cell division, during which it protects cells against fluctuations in ER demand.

...cytokinesis requires UPR activation to progress...

The authors observed that the UPR was activated in unstressed budding yeast cells. To uncover the cause of this moderate level of UPR activation, Bicknell et al. studied ER-stressed cells and looked for cellular processes that were sensitive to ER stress. ER-stressed cells grew normally at early time points, but progressively contained larger amounts of DNA compared with unstressed cells and often had multibudded morphologies. This phenotype suggested that ER stress does not block DNA replication, but that it inhibits cell division — possibly during late mitosis or cytokinesis. The former possibility was ruled out by studying indicators of mitotic exit: the degradation of Clb2 and the cytoplasmic relocation of Cdc14 that mark mitotic exit were unaffected in ER-stressed cells, as was spindle disassembly.

To confirm that cytokinesis requires UPR activation to progress, the authors studied a UPR-defective yeast mutant strain. Cytokinesis was inefficient and was delayed even in the absence of any external ER-stress inducers. Therefore, it seems that cytokinesis places a demand on the ER — perhaps because of a requirement for membrane vesicles or phospholipids from the secretory pathway that are used in the pinching process. The authors propose that cytokinesis may be one of several physiological processes that induce moderate levels of UPR signalling to fine-tune the capacity of the ER to the dynamic cellular environment.