EVIDENCE FOR A SECRETORY FORM OF THE CELLULAR PRION PROTEIN
EVIDENCE FOR A SECRETORY FORM OF THE CELLULAR PRION PROTEIN
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DOI：
10.1021/bi00399a014
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发表时间：
1987-12-15
期刊：
影响因子：
2.9
通讯作者：
LINGAPPA, VR
中科院分区：
文献类型：
--
作者：
HAY, B;PRUSINER, SB;LINGAPPA, VR
通过在非洲爪哇卵母细胞和无细胞系统中表达全长PrP基因转录的RNA，研究了仓鼠脑PrP蛋白的生物发生。早期在小麦胚芽无细胞系统中的研究表明，PrP的一种形式是一种跨膜蛋白，它至少两次跨越双层[Hay，B.，Barry，R.A.，Lieberburg，I.，Prusiner，S.B.和Lingappa，V.R.(1987)Mol.牢房。比奥尔。7,914-920]。我们现在报告PrP也可以作为一种分泌性蛋白质存在。将SP6PrP RNA显微注射到非洲爪哇卵母细胞中，产生两种形式的PrP：一种留在细胞内，另一种分泌到培养液中。在添加了微粒体膜的兔网织红细胞裂解物中进行的无细胞翻译研究得到了类似的结果：一种形式的PrP被发现为至少两次跨膜的完整膜蛋白，而另一种形式的PrP被发现完全移位到微粒体膜泡腔。PrP的膜和分泌型似乎都是从同一个新生链池中产生的。控制新生PrP命运变化的机制仍有待阐明，但可能对理解瘙痒病和其他Pron疾病的发病机制具有重要意义。
The biogenesis of hamster brain prion protein (PrP) has been studied by expression of RNA transcribed from a full-length PrP cDNA in Xenopus oocytes and cell-free systems. Earlier studies in the wheat germ cell-free system showed that one form of PrP is a transmembrane protein that spans the bilayer at least twice [Hay, B., Barry, R. A., Lieberburg, I., Prusiner, S. B., and Lingappa, V. R. (1987) Mol. Cell. Biol. 7, 914-920]. We now report that PrP can also exist as a secreted protein. SP6 PrP RNA microinjected into Xenopus oocytes produced two forms of PrP: one that remained in the cell and another that was secreted into the medium. Cell-free translation studies in rabbit reticulocyte lysates supplemented with microsomal membranes gave similar results: while one form of PrP was found as an integral membrane protein spanning the membrane at least twice, another form of PrP was found to be completely translocated to the microsomal membrane vesicle lumen. Both the membrane and secretory forms of PrP appear to be generated from the same pool of nascent chains. The mechanism governing the alternative fates of nascent PrP remains to be elucidated but may have significance for understanding the pathogenesis of scrapie and other prion diseases.