Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions. Yeast prions, including the best studied ones ([PSI ] and [URE3]), propagate via intimate interactions with molecular chaperones. Different yeast prions exhibit differential responses to changes in levels, functionality or localization of the components of chaperone machinery. Here, we provide additional data confirming differential effects of chaperones (and specifically, Hsp40s) on yeast prions and summarize current knowledge of the mechanisms underlying chaperone specificities. Contrary to frequent statements in literature, overproduction of the Hsp104 chaperone antagonizes both [PSI] and [URE3] prions, while overproduction of the Hsp70-Ssa1 chaperone antagonizes [URE3] prion only in some, but not in all strains. Recently, we demonstrated that the relocalization of a fraction of the Hsp40 chaperone Sis1 from the cytosol to the nucleus by the chaperone-sorting factor Cur1 exhibits opposite effects on [PSI ] and [URE3] prions. We suggest that the response of prions to changes in Sis1 localization represents a combination of the effects of Sis1 shortage on fragmentation of prion aggregates and on malpartition of prion aggregates during a cell division. Differences in sensitivity of prion fragmentation to Sis1 and in relative inputs of fragmentation and malpartition in prion propagation result in opposite effects of Sis1 relocalization on [PSI] and [URE3].

Active accumulation of the data on new amyloids continuing nowadays dissolves boundaries of the term “amyloid”. Currently, it is most often used to designate aggregates with cross-β structure. At the same time, amyloids also exhibit a number of other unusual properties, such as: detergent and protease resistance, interaction with specific dyes, and ability to induce transition of some proteins from a soluble form to an aggregated one. The same features have been also demonstrated for the aggregates lacking cross-β structure, which are commonly called “amyloid-like” and combined into one group, although they are very diverse. We have collected and systematized information on the properties of more than two hundred known amyloids and amyloid-like proteins with emphasis on conflicting examples. In particular, a number of proteins in membraneless organelles form aggregates with cross-β structure that are morphologically indistinguishable from the other amyloids, but they can be dissolved in the presence of detergents, which is not typical for amyloids. Such paradoxes signify the need to clarify the existing definition of the term amyloid. On the other hand, the demonstrated structural diversity of the amyloid-like aggregates shows the necessity of their classification.

Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI ]. We demonstrate that both curing of [URE3] and enhancement of [PSI ] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.