title: Chaperone proteins select and maintain [PIN+] prion conformations in Saccharomyces cerevisiae.
abstract: Prions are proteins that can adopt different infectious conformations known as "strains" or "variants," each with a distinct, epigenetically inheritable phenotype. Mechanisms by which prion variants are determined remain unclear. Here we use the Saccharomyces cerevisiae prion Rnq1p/[PIN(+)] as a model to investigate the effects of chaperone proteins upon prion variant determination. We show that deletion of specific chaperone genes alters [PIN(+)] variant phenotypes, including [PSI(+)] induction efficiency, Rnq1p aggregate morphology/size and variant dominance. Mating assays demonstrate that gene deletion-induced phenotypic changes are stably inherited in a non-Mendelian manner even after restoration of the deleted gene, confirming that they are due to a bona fide change in the [PIN(+)] variant. Together, our results demonstrate a role for chaperones in regulating the prion variant complement of a cell.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. dll1@ualberta.ca
authors.forename: David L
authors.initials: DL
authors.lastname: Lancaster
authors.forename: C Melissa
authors.initials: CM
authors.lastname: Dobson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rachubinski
mesh_terms: D018833:Chaperonins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D008954:Models, Biological; D010957:Plasmids; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D011328:Prions; D018833:Chaperonins