Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

The Journal of Biological Chemistry
Xiaohong ZhaoLois E Greene

Abstract

Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

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Citations

Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Leslie RipaudMark S Hipp
Dec 18, 2015·Scientific Reports·Genrikh V SerpionovMichael D Ter-Avanesyan
Jun 12, 2013·The Biochemical Journal·Kuljit SinghIpsita Roy
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Mar 30, 2018·Frontiers in Molecular Neuroscience·Meenakshi VermaVibha Taneja
Aug 24, 2021·Molecular and Cellular Biology·Nicole J WayneLois E Greene

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Methods Mentioned

BETA
PCR
confocal microscopy

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