Whi3 Mnemon Association with Endoplasmic Reticulum Membranes Confines the Memory of Deceptive Courtship to the Yeast Mother Cell

Abstract

Prion-like proteins are involved in many aspects of cellular physiology, including cellular memory. In response to deceptive courtship, budding yeast escapes pheromone induced cell cycle arrest through coalescence of the G1/S inhibitor Whi3 into a dominant, inactive super-assembly. Whi3 is a mnemon (Whi3mnem), a protein which conformational change maintains a trait in the mother cell but is not inherited by daughter cells. 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 lateral diffusion barriers present at the bud neck. Strikingly, barrier defects made Whi3mnem propagate in a mitotically stable, prion-like manner. The amyloid forming glutamine-rich domain of Whi3 was required for both mnemon and prion-like behaviours. Thus, we propose that Whi3mnem is in a self-templating state, lending temporal maintenance of memory, while its association with the compartmentalized membranes of the ER prevents infectious propagation to daughter cells. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information and its retention by individual cells upon division. Yeast courtship may provide insights for how individual synapses become potentiated in neuronal memory.