Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform.
Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform.
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DOI：
10.1083/jcb.129.1.121
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发表时间：
1995-04
影响因子：
7.8
通讯作者：
PRUSINER, SB
中科院分区：
文献类型：
--
作者：
TARABOULOS, A;SCOTT, M;SEMENOV, A;AVRAHAM, D;LASZLO, L;PRUSINER, SB
PrPC被糖磷脂酰肌醇(GPI)锚点结合到细胞表面后，PrPC被代谢或转化为瘙痒异构体(PrPSc)。由于大多数GPI锚定蛋白与富含胆固醇的膜微域相关，我们询问这些结构是否参与PrPC的代谢或PrPSc的形成。PrPC的初始降解包括去除PrPC的NH2末端以产生17-kD的多肽，该多肽存在于Triton X-100的不溶部分中。洛伐他汀可抑制PrPSc的形成和PrPC的初始降解，但对NH4Cl不敏感。17-kD多肽的进一步降解确实发生在对NH4Cl敏感的酸性隔间中。用小鼠CD4的跨膜区和胞浆区取代GPI添加信号，使嵌合的CD4PrPC可溶于冷的Triton X-100。没有GPI相加信号的CD4PrPC和截断PrPC(Rogers，M.，F.Yehieley，M.Scott和S.B.Prusiner)。1993年。程序娜塔莉。阿卡德。SCI。美国。90：3182-3186)是形成PrPSc的较差底物。因此，PrPC的初始降解为17-kD多肽和PrPSc的形成似乎都发生在由富含胆固醇的膜(可能是富含糖脂的微域)结合的非酸性隔室中，PrPC的代谢命运在那里被决定。17-kD多肽和PrPSc被运输到酸性隔间的途径仍有待确定，推测是内小体，在那里17-kD多肽被水解，PrPSc有限的蛋白分解产生PrP27-30。
After the cellular prion protein (PrPC) transits to the cell surface where it is bound by a glycophosphatidyl inositol (GPI) anchor, PrPC is either metabolized or converted into the scrapie isoform (PrPSc). Because most GPI-anchored proteins are associated with cholesterol-rich membranous microdomains, we asked whether such structures participate in the metabolism of PrPC or the formation of PrPSc. The initial degradation of PrPC involves removal of the NH2 terminus of PrPC to produce a 17-kD polypeptide which was found in a Triton X-100 insoluble fraction. Both the formation of PrPSc and the initial degradation of PrPC were diminished by lovastatin-mediated depletion of cellular cholesterol but were insensitive to NH4Cl. Further degradation of the 17-kD polypeptide did occur within an NH4Cl-sensitive, acidic compartment. Replacing the GPI addition signal with the transmembrane and cytoplasmic domains of mouse CD4 rendered chimeric CD4PrPC soluble in cold Triton X-100. Both CD4PrPC and truncated PrPC without the GPI addition signal (Rogers, M., F. Yehieley, M. Scott, and S. B. Prusiner. 1993. Proc. Natl. Acad. Sci. USA. 90:3182-3186) were poor substrates for PrPSc formation. Thus, it seems likely that both the initial degradation of PrPC to the 17-kD polypeptide and the formation of PrPSc occur within a non-acidic compartment bound by cholesterol-rich membranes, possibly glycolipid-rich microdomains, where the metabolic fate of PrPC is determined. The pathway remains to be identified by which the 17-kD polypeptide and PrPSc are transported to an acidic compartment, presumably endosomes, where the 17-kD polypeptide is hydrolyzed and limited proteolysis of PrPSc produces PrP 27-30.
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在培养细胞中的合成和拓扑的动力学方面，crap和细胞prion蛋白不同。
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
影响因子：
5.4
作者：
KASCSAK, RJ;RUBENSTEIN, R;DIRINGER, H
通讯作者：
DIRINGER, H
DOI：
10.1083/jcb.118.1.63
发表时间：
1992-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chang WJ;Rothberg KG;Kamen BA;Anderson RG
通讯作者：
Anderson RG
影响因子：
5.4
作者：
BUTLER, DA;SCOTT, MRD;PRUSINER, SB
通讯作者：
PRUSINER, SB
DOI：
10.1073/pnas.88.17.7664
发表时间：
1991-09-01
影响因子：
11.1
作者：
HARRIS, DA;FALLS, DL;FISCHBACH, GD
通讯作者：
FISCHBACH, GD