Prions are self-perpetuating misfolded proteins that can be passed during cell division. De novo formation of yeast prions naturally occurs at an extremely low frequency. Yet, increasing the level of the prion protein can induce higher prion frequencies, presumably because the abundance of protein molecules makes it more likely that a small percentage of proteins misfold and form prions. Using the prion [PSI+], which is the misfolded version of the Sup35p translation termination protein, prion formation can be monitored by transiently over expressing the prion domain of Sup35p fused to GFP. A notable early hallmark of prion induction is the formation of cytoplasmic fluorescent rings. These ring-like structures are retained in the mother cell, and prion induction is dependent upon inheritance of prion particles by the daughter cells. Our previous work identified several genes that reduced prion induction. These genes fell into two groups: the first affects ring formation, and the second appears to be involved in later events after the ring has formed. Since most of the genes identified encoded proteins associated with the actin cytoskeleton, we further investigated the role of actin in prion formation. We found that low levels of the actin cable-disrupting drug, Latrunculin A, had no effect on ring formation, but increased prion induction frequency. Similar effects were identified in an actin mutant with documented cable defects, act1-101, suggesting that actin cables are important for later stages of prion formation. It was previously shown that altered actin networks in strains lacking SIR2 reduce the asymmetrical retention of damaged proteins to the mother cell. To explore whether the actin effects on prion induction are due to spatial quality control, we induced prion formation in sir2D strains. We found that ring formation was again unaffected in sir2D strains, but prion induction frequency was significantly increased. Taken together, our data suggests that later prion events are dependent upon the ability to overcome spatial quality control mechanisms.