Inhibition of cholesterol recycling impairs cellular PrP(Sc) propagation.
Inhibition of cholesterol recycling impairs cellular PrP(Sc) propagation.
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DOI：
10.1007/s00018-009-0158-4
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发表时间：
2009-12
影响因子：
8
通讯作者：
Schatzl, Hermann M.
中科院分区：
文献类型：
--
作者：
Gilch, Sabine;Bach, Christian;Lutzny, Gloria;Vorberg, Ina;Schatzl, Hermann M.
The infectious agent in prion diseases consists of an aberrantly folded isoform of the cellular prion protein (PrPc), termed PrPSc, which accumulates in brains of affected individuals. Studies on prion-infected cultured cells indicate that cellular cholesterol homeostasis influences PrPSc propagation. Here, we demonstrate that the cellular PrPSc content decreases upon accumulation of cholesterol in late endosomes, as induced by NPC-1 knock-down or treatment with U18666A. PrPc trafficking, lipid raft association, and membrane turnover are not significantly altered by such treatments. Cellular PrPSc formation is not impaired, suggesting that PrPSc degradation is increased by intracellular cholesterol accumulation. Interestingly, PrPSc propagation in U18666A-treated cells was partially restored by overexpression of rab 9, which causes redistribution of cholesterol and possibly of PrPSc to the trans-Golgi network. Surprisingly, rab 9 overexpression itself reduced cellular PrPSc content, indicating that PrPSc production is highly sensitive to alterations in dynamics of vesicle trafficking. The online version of this article (doi:10.1007/s00018-009-0158-4) contains supplementary material, which is available to authorized users.
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DOI：
10.1083/jcb.110.3.743
发表时间：
1990-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Borchelt DR;Scott M;Taraboulos A;Stahl N;Prusiner SB
通讯作者：
Prusiner SB
DOI：
10.1073/pnas.0503689102
发表时间：
2005-09-20
影响因子：
11.1
作者：
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通讯作者：
Willnow, TE
影响因子：
4.2
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通讯作者：
Gabizon, Ruth
影响因子：
3.3
作者：
Choudhury, A;Sharma, DK;Pagano, RE
通讯作者：
Pagano, RE
影响因子：
4.8
作者：
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通讯作者：
Lehmann, S