Curing of the [URE3] prion by Btn2p, a Batten disease-related protein.
[URE3] is a prion (infectious protein), a self-propagating amyloid form of Ure2p, a regulator of yeast nitrogen catabolism. We find that overproduction of Btn2p, or its homologue Ypr158 (Cur1p), cures [URE3]. Btn2p is reported to be associated with late endosomes and to affect sorting of several proteins. We find that double deletion of BTN2 and CUR1 stabilizes [URE3] against curing by several agents, produces a remarkable increase in the proportion of strong [URE3] variants arising de novo and an increase in the number of [URE3] prion seeds. Thus, normal levels of Btn2p and Cur1p affect prion generation and propagation. Btn2p-green fluorescent protein (GFP) fusion proteins appear as a single dot located close to the nucleus and the vacuole. During the curing process, those cells having both Ure2p-GFP aggregates and Btn2p-RFP dots display striking colocalization. Btn2p curing requires cell division, and our results suggest that Btn2p is part of a system, reminiscent of the mammalian aggresome, that collects aggregates preventing their efficient distribution to progeny cells.
Kryndushkin
Dmitry S
DS
Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
Shewmaker
Frank
F
Wickner
Reed B
RB
D026905:Amino Acid Transport Systems / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005979:Glutathione Peroxidase; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology; D010957:Plasmids / Q000378:metabolism; D011328:Prions / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D033921:Vesicular Transport Proteins; D050888:Heat-Shock Proteins, Small
D026905:Amino Acid Transport Systems; D005656:Fungal Proteins; D005979:Glutathione Peroxidase; D049452:Green Fluorescent Proteins; D018832:Molecular Chaperones; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; C473804:BTN2 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D050888:Heat-Shock Proteins, Small; C532957:CUR1 protein, S cerevisiae; C067020:URE2 protein, S cerevisiae