Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes
Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of pr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/66126 https://orcid.org/0000-0003-1307-882X |
| _version_ | 1826193200289677312 |
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| author | Manogaran, Anita L. Hong, Joo Y. Hufana, Joan Tyedmers, Jens Lindquist, Susan Liebman, Susan W. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Manogaran, Anita L. Hong, Joo Y. Hufana, Joan Tyedmers, Jens Lindquist, Susan Liebman, Susan W. |
| author_sort | Manogaran, Anita L. |
| collection | MIT |
| description | Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI+] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN+]. When fused to GFP and overexpressed in [ps−] [PIN+] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI+] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI+]. Two classes of gene deletions were identified. Class I deletions (bug1Δ, bem1Δ, arf1Δ, and hog1Δ) reduced the efficiency of [PSI+] induction, but formed rings normally. Class II deletions (las17Δ, vps5Δ, and sac6Δ) inhibited both [PSI+] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington's disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps. |
| first_indexed | 2024-09-23T09:35:31Z |
| format | Article |
| id | mit-1721.1/66126 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:35:31Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
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| spelling | mit-1721.1/661262022-09-30T15:29:58Z Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes Manogaran, Anita L. Hong, Joo Y. Hufana, Joan Tyedmers, Jens Lindquist, Susan Liebman, Susan W. Massachusetts Institute of Technology. Department of Biology Lindquist, Susan Lindquist, Susan Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast. While much work has focused around chaperones involved in prion maintenance, including Hsp104, little is known about factors involved in the appearance of prions. De novo appearance of the [PSI+] prion, which is the aggregated form of the Sup35 protein, is dramatically enhanced by transient overexpression of SUP35 in the presence of the prion form of the Rnq1 protein, [PIN+]. When fused to GFP and overexpressed in [ps−] [PIN+] cells, Sup35 forms fluorescent rings, and cells with these rings bud off [PSI+] daughters. We investigated the effects of over 400 gene deletions on this de novo induction of [PSI+]. Two classes of gene deletions were identified. Class I deletions (bug1Δ, bem1Δ, arf1Δ, and hog1Δ) reduced the efficiency of [PSI+] induction, but formed rings normally. Class II deletions (las17Δ, vps5Δ, and sac6Δ) inhibited both [PSI+] induction and ring formation. Furthermore, class II deletions reduced, while class I deletions enhanced, toxicity associated with the expanded glutamine repeats of the huntingtin protein exon 1 that causes Huntington's disease. This suggests that prion formation and polyglutamine aggregation involve a multi-phase process that can be inhibited at different steps. National Institutes of Health (U.S.) (grant GM56350) National Institutes of Health (U.S.) (NSRA F32 postdoctoral fellowship GM072340) National Institutes of Health (U.S.) (grant GM25874) Howard Hughes Medical Institute 2011-09-30T12:40:14Z 2011-09-30T12:40:14Z 2011-05 2010-07 Article http://purl.org/eprint/type/JournalArticle 1553-7404 1553-7390 http://hdl.handle.net/1721.1/66126 Manogaran AL, Hong JY, Hufana J, Tyedmers J, Lindquist S, et al. (2011) Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes. PLoS Genet 7(5): e1001386. doi:10.1371/journal.pgen.1001386 https://orcid.org/0000-0003-1307-882X en_US http://dx.doi.org/10.1371/journal.pgen.1001386 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Manogaran, Anita L. Hong, Joo Y. Hufana, Joan Tyedmers, Jens Lindquist, Susan Liebman, Susan W. Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title | Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title_full | Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title_fullStr | Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title_full_unstemmed | Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title_short | Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes |
| title_sort | prion formation and polyglutamine aggregation are controlled by two classes of genes |
| url | http://hdl.handle.net/1721.1/66126 https://orcid.org/0000-0003-1307-882X |
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