Actin impacts the late stages of prion formation and prion propagation

Abstract

AbstractIn yeast, the [PSI+] and [PIN+] prions are aggregated forms of the Sup35 and Rnq1 proteins, respectively. The cellular mechanisms that underlie the formation and propagation of these prion states are not clearly understood. Our previous work suggested that actin networks play a role in early and late steps of the formation of [PSI+]. To further explore how actin impacts yeast prions, we turned to a set of actin point mutants. We found that the disruption of actin cables, either by an actin destabilizing drug or the act1-101 mutant, can enhance prion formation during the later stages of prion formation. Our data suggest that under normal conditions, actin cables play a role in limiting the inheritance of newly made prion particles to daughter cells. We also found actin can impact prion propagation. The act1-122 mutant, which contains a substitution in the fimbrin binding region, destabilized the [PIN+] prion over time. This is the first evidence that actin has a role in [PIN+] propagation. Taken together, our findings reveal novel roles for actin in the formation and propagation of prions.