Regardless of whether they bud from young or old mothers, Saccharomyces cerevisiae daughter cells are capable of undergoing roughly the same number of subsequent divisions. This resetting of daughter cells' biological clocks is attributed to the formation of a diffusion barrier at the bud neck that contains ageing factors in the mother cell. Barral and colleagues provide insight into the nature and function of this barrier (eLife 3, e01883; 2014).
Misfolded proteins formed as a result of endoplasmic reticulum (ER) stress were specifically retained in the mother cell by a sphingolipid-rich ER diffusion barrier. Intriguingly, proteins involved in bud site selection — including the GTPase Bud1, the GEF Cdc24 and the GTPase Cdc42 — were essential for diffusion barrier formation and the retention of misfolded proteins in the mother cell. ER stress reduces replicative lifespan, but bud1Δ cells were largely protected from this effect, suggesting that the diffusion barrier normally acts to contain toxic misfolded proteins within the mother cell.
The authors also found that the sphingolipid diffusion barrier forms downstream of the known barrier components septin and Bud6, and that sphingolipids help to define a discrete ER membrane subdomain in the bud neck. These findings add complexity to the composition and function of diffusion barriers, and suggest that the ER barrier has a fundamental role in keeping daughter cells young.