Chaperone networks are required for the shearing and generation of transmissible propagons from pre‐existing prion aggregates. However, other cellular networks needed for maintaining yeast prions are largely uncharacterized. Here, we establish a novel role for actin networks in prion maintenance. The [PIN +] prion, also known as [RNQ +], exists as stable variants dependent upon the chaperone machinery for the transmission of propagons to daughter cells during cell division and cytoplasmic transfer. Loss of the Hsp104 molecular chaperone leads to the growth of prion particles until they are too large to be transmitted. Here, we isolated a unique [PIN +] variant, which is unstable in actin mutants. This prion loss is observed over many generations, and coincides with the detection of both high molecular weight species of Rnq1 and large visible aggregates that are asymmetrically retained during cell division. Our data suggest that the irregular actin networks found in these mutants may influence propagon number by slowly permitting aggregate growth over time, resulting in the generation of nontransmissible large aggregates. Thus, we show the potential contribution of cytoskeletal networks in the transmission of prion propagons, which parallels models that have been proposed for cell‐to‐cell transmission of small amyloids in neurodegenerative protein aggregation diseases.
Dorweiler, Jane E.; Oddo, Mitchell J.; Lyke, Douglas R.; Reilly, Jacob A.; Wisniewski, Brett T.; Davis, Emily E.; Kuborn, Abigail M.; Merrill, Stephen J.; and Manogaran, Anita L., "The Actin Cytoskeletal Network Plays a Role in Yeast Prion Transmission and Contributes to Prion Stability" (2020). Biological Sciences Faculty Research and Publications. 835.