Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.

<h4>Background</h4>Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamin...

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Autores principales:	Natalia V Kochneva-Pervukhova, Alexander I Alexandrov, Michael D Ter-Avanesyan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a126f683c7864c849bda5424748fc5ef
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spelling	oai:doaj.org-article:a126f683c7864c849bda5424748fc5ef2021-11-18T07:30:28ZAmyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.1932-620310.1371/journal.pone.0029832https://doaj.org/article/a126f683c7864c849bda5424748fc5ef2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253794/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain.<h4>Principal findings</h4>Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast.<h4>Conclusions</h4>The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity.Natalia V Kochneva-PervukhovaAlexander I AlexandrovMichael D Ter-AvanesyanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29832 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalia V Kochneva-Pervukhova Alexander I Alexandrov Michael D Ter-Avanesyan Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
description	<h4>Background</h4>Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain.<h4>Principal findings</h4>Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast.<h4>Conclusions</h4>The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity.
format	article
author	Natalia V Kochneva-Pervukhova Alexander I Alexandrov Michael D Ter-Avanesyan
author_facet	Natalia V Kochneva-Pervukhova Alexander I Alexandrov Michael D Ter-Avanesyan
author_sort	Natalia V Kochneva-Pervukhova
title	Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
title_short	Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
title_full	Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
title_fullStr	Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
title_full_unstemmed	Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
title_sort	amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a126f683c7864c849bda5424748fc5ef
work_keys_str_mv	AT nataliavkochnevapervukhova amyloidmediatedsequestrationofessentialproteinscontributestomutanthuntingtintoxicityinyeast AT alexanderialexandrov amyloidmediatedsequestrationofessentialproteinscontributestomutanthuntingtintoxicityinyeast AT michaeldteravanesyan amyloidmediatedsequestrationofessentialproteinscontributestomutanthuntingtintoxicityinyeast
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Amyloid-mediated sequestration of essential proteins contributes to mutant huntingtin toxicity in yeast.

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