Disrupting the cortical actin cytoskeleton points to two distinct mechanisms of yeast [PSI+] prion formation

摘要: Mammalian and fungal prions arise de novo; however, the mechanism is poorly understood in molecular terms. One strong possibility that oxidative damage to non-prion form of a protein may be an important trigger influencing formation its heritable prion conformation. We have examined stress-induced yeast [PSI+] prion, which altered conformation Sup35 translation termination factor. used tandem affinity purification (TAP) mass spectrometry identify proteins associate with tsa1 tsa2 antioxidant mutant address by forms during stress conditions. This analysis identified several components cortical actin cytoskeleton including Abp1 nucleation promoting factor, we show deletion ABP1 gene abrogates oxidant-induced formation. The frequency spontaneous can increased overexpression since excess increases probability forming seeds. In contrast formation, overexpression-induced was only modestly affected abp1 mutant. Furthermore, treating cells latrunculin A disrupt cables patches abrogated oxidant-induced, but not suggesting mechanistic difference [PIN+], Rnq1, localizes IPOD (insoluble deposit) thought influence aggregation other proteins. becomes oxidized aggregates conditions, does co-localize Rnq1 account for reduced