Destabilizing interactions among [PSI(+)] and [PIN(+)] yeast prion variants

The yeast Sup35 and Rnq1 proteins can exist in either the noninfectious soluble forms, psi-] or pin-], respectively, or the multiple infectious amyloid-like forms called PSI+] or PIN+] prion variants (or prion strains). It was previously shown that PSI+] and PIN+] prions enhance one another's de novo appearance. Here we show that specific prion variants of PSI+] and PIN+] disrupt each other's stable inheritance. Acquiring PSI+] often impedes the inheritance of particular PIN+] variants. Conversely, the presence of some PIN+] variants impairs the inheritance of weak PSI+] but not strong PSI+] variants. These same PIN+] variants generate a single-dot fluorescence pattern when a fusion of Rnq1 and green fluorescent protein is expressed. Another PIN+] variant, which forms a distinctly different multiple-dot fluorescence pattern, does not impair PSI+] inheritance. Thus, destabilization of prions by heterologous prions depends upon the variants involved. These findings may have implications for understanding interactions among other amyloid-forming proteins, including those associated with certain human diseases.