Whi3 mnemon association with endoplasmic reticulum membranes confines the memory of deceptive courtship to the yeast mother cell

Yasmin Lau,Henry Patrick Oamen,Marcel Grogg,Iuliia Parfenova,Juha Saarikangas,Robin Hannay,Richard Alan Nichols,Donald Hilvert,Yves Barral,Fabrice Caudron

doi:10.1016/j.cub.2022.01.002

Yasmin Lau, Henry Patrick Oamen + Show 8 more

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https://doi.org/10.1016/j.cub.2022.01.002

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Abstract

SummaryPrion-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 the coalescence of the G1/S inhibitor Whi3 into a dominant, inactive super-assembly. Whi3 is a mnemon (Whi3mnem), a protein that conformational change maintains as a trait in the mother cell but is not inherited by the 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 is retained in the mother cell by the 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 behaviors. Thus, we propose that Whi3mnem is in a self-templating state, lending temporal maintenance of memory, whereas its association with the compartmentalized membranes of the ER prevents infectious propagation to the daughter cells. These results suggest that confined self-templating super-assembly is a powerful mechanism for the long-term encoding of information in a spatially defined manner. Yeast courtship may provide insights on how individual synapses become potentiated in neuronal memory.

Highlights

Prions are proteins that can adopt several conformations, at least one of which is self-templating, lending it a self-perpetuating character and supporting its propagation in the cell population, or even across individuals, in an infectious-like manner
Prion-like proteins are involved in many aspects of cellular physiology, including cellular memory
Whi[3] is a mnemon (Whi3mnem), a protein that conformational change maintains as a trait in the mother cell but is not inherited by the daughter cells

Summary

Introduction

Prions are proteins that can adopt several conformations, at least one of which is self-templating, lending it a self-perpetuating character and supporting its propagation in the cell population, or even across individuals, in an infectious-like manner. Recent studies reveal the role of prion-like proteins in spatially defined processes, i.e., where conversion is not associated with an infectious-like propagation of the protein. Such an instance occurs during the response of yeast cells to pheromone: upon the detection of the pheromone produced by the cells of the opposite mating type, haploid yeast cells arrest in the G1 phase of the cell cycle and grow toward the source of this signal. Yeast courtship provides a simple model for studying how single cells keep memory of past events and use this information to individually adapt their behavior to their environment

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