Extracellular Vesicles-Encapsulated Yeast Prions and What They Can Tell Us about the Physical Nature of Propagons

Abstract

The yeast Saccharomyces cerevisiae hosts an ensemble of protein-based heritable traits, most of which result from the conversion of structurally and functionally diverse cytoplasmic proteins into prion forms. Among these, [PSI+], [URE3] and [PIN+] are the most well-documented prions and arise from the assembly of Sup35p, Ure2p and Rnq1p, respectively, into insoluble fibrillar assemblies. Yeast prions propagate by molecular chaperone-mediated fragmentation of these aggregates, which generates small self-templating seeds, or propagons. The exact molecular nature of propagons and how they are faithfully transmitted from mother to daughter cells despite spatial protein quality control are not fully understood. In [PSI+] cells, Sup35p forms detergent-resistant assemblies detectable on agarose gels under semi-denaturant conditions and cytosolic fluorescent puncta when the protein is fused to green fluorescent protein (GFP); yet, these macroscopic manifestations of [PSI+] do not fully correlate with the infectivity measured during growth by the mean of protein infection assays. We also discovered that significant amounts of infectious Sup35p particles are exported via extracellular (EV) and periplasmic (PV) vesicles in a growth phase and glucose-dependent manner. In the present review, I discuss how these vesicles may be a source of actual propagons and a suitable vehicle for their transmission to the bud.

Immunomodulatory Potential of Fungal Extracellular Vesicles: Insights for Therapeutic Applications

“…C. neoformans EVs were also found to carry melanin in an older study [145]. Prions have been found in EVs from S. cerevisiae, both in soluble and aggregated forms [24,125], and it has been hypothesised that they can play a role in vertical and horizontal transmission [146].…”

Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures

“…Second, transitions among these structures may reflect changes in sub-cellular localization, exacerbated by alterations in cellular environments and the state of stress over the experimental regime. For example, proteasome inhibition, elevated temperature, and other stresses induce misfolded proteins, including the amyloidogenic proteins associated with the [ PSI + ], [ PIN + ] and HET-s prions [ 108 ], to form single foci at the insoluble protein deposit (IPOD) or juxta nuclear quality control compartment (JUNQ) [ 111 ], while glucose limitation promotes packaging of both monomeric and aggregated Sup35 in extracellular [ 112 ] as well as periplasmic vesicles [ 113 ]. Intriguingly, the Sup35 PrD interacts with cytoskeletal components and is at the yeast aggresome, [ 114 ] and the treatment of a [ PSI + ] strain with LatA makes PrD-GFP adopt a diffuse pattern [ 115 ].…”

How Big Is the Yeast Prion Universe?

“…Since then, many new prions and prion-like proteins have been identified in yeast. Several recent reviews have focused on yeast prions [11][12][13][14][15][16][17][18][19]. Here, we provide a brief overview of the yeast prions found so far and focus our attention to the various approaches used to identify them.…”