Résumé
In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging. DOI:
http://dx.doi.org/10.7554/eLife.01883.001 Cell division isn't always about splitting a cell into two identical parts. The diversity of many of our own cells relies on asymmetric cell divisions. The yeast used to make bread rely on a process called ‘budding’ that involves a small daughter cell emerging from the surface of the mother cell. Mother cells can only produce around 20–50 daughter cells before dying from old age. However, their daughters are always born rejuvenated, and not aged like their mothers. Budding involves part of the plasma membrane that surrounds the mother cell being pinched off to produce the daughter cell. This part of the membrane contains diffusion barriers that prevent various factors—including factors that cause aging—from entering the daughter cell. The barriers are known to contain several layers, but the details of how they work were not understood. Inside the budding cell, the membrane of the endoplasmic reticulum (ER) also contains lateral diffusion barriers. The ER is the structure in the cell responsible for folding newly made proteins correctly. Any misfolded, toxic proteins are kept in the ER to be refolded or destroyed. However, if there are too many misfolded proteins, the ER gets stressed and triggers a mechanism that in extreme cases causes the cell to self-destruct. Clay, Caudron et al. have now shown that ER stress causes yeast cells to age. Moreover, when the ER is stressed, the ER diffusion barrier prevents the stress that causes aging entering the daughter cells. Clay, Caudron et al. also established that the diffusion barrier in the ER is made up of three layers. A layer of fatty molecules called sphingolipids is found at the bottom of the barrier, and such a layer is also present in other diffusion barriers. This could therefore act as the skeleton on which diffusion barriers form. Further investigation of this layer should provide a better understanding of how diffusion barriers work. DOI:
http://dx.doi.org/10.7554/eLife.01883.002