Journal
CURRENT BIOLOGY
Volume 32, Issue 5, Pages 963-+Publisher
CELL PRESS
DOI: 10.1016/j.cub.2022.01.002
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Funding
- Biotechnology and Biological Sciences Research Council [BB/S001204/1]
- QMUL
- MUSE
- Academy of Finland [317038]
- European Research Council [BarrAge 250278]
- ETH Zurich
- Sigrid Juselius Foundation
- Academy of Finland (AKA) [317038, 317038] Funding Source: Academy of Finland (AKA)
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This study found that Whi3(mnem) is closely associated with endoplasmic reticulum (ER) membranes and is retained in the mother cell by the lateral diffusion barriers at the bud neck. When there were defects in the barriers, Whi3(mnem) propagated in a prion-like manner. The amyloid-forming domain of Whi3 was crucial for both memory and prion-like behaviors. The results suggest that confined self-templating super-assembly is a powerful mechanism for encoding information in a spatially defined manner.
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 the coalescence of the G1/S inhibitor Whi3 into a dominant, inactive super-assembly. Whi3 is a mnemon (Whi3(mnem)), 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 Whi3(mnem) are achieved is unknown. Here, we report that Whi3(mnem) 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 Whi3(mnem) 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 Whi3(mnem) 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.
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