Abstract
In response to deceptive courtship, budding yeast cells escape pheromone induced cell cycle arrest through coalescence of the G1/S inhibitor Whi3 into a dominant inactive super-assembly. Strikingly, Whi3 super-assemblies remain stable over many cell cycles in the mother cells and are not passed on to the daughter cells. Thereby, Whi3 coalescence encodes memory, conferring to it the property of a mnemon (Whi3mnem), a protein which conformational change maintain a trait that is permanent in the mother cell but is not inherited by daughter cells. Mnemons share structural features with prions, which are self-templating protein conformations that are inherited by daughter cells. Yet, how the maintenance and asymmetric inheritance of Whi3mnem are achieved is unknown. Here, we report that Whi3mnem is closely associated with endoplasmic reticulum (ER) membranes and retained in the mother cell by the presence of lateral membrane diffusion barriers at the bud neck. Strikingly, barrier defects made Whi3mnem propagate in a mitotically stable manner, like a prion. Alike Whi3mnem, transformation of Whi3 into a prion required its poly-glutamine prion-like domain. Thus, we propose that Whi3mnem is in a self-templating state, lending temporal stability to the memory that it encodes, while its anchorage into the compartmentalized membranes of the ER ensures its confinement in the mother cell and prevents its infectious propagation. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information.
Footnotes
Figure 1 now includes a new analysis of the Constitutive Escapers frequencies. RA Nichols who did this work is added as an author.