Arnold J E, Tipler C, Laszlo L, Hope J, Landon M, Mayer R J
Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.
J Pathol. 1995 Aug;176(4):403-11. doi: 10.1002/path.1711760412.
The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie-infected mouse brain was used to show, both biochemically and by double-labelled immunogold electron microscopy, that proteinase K-resistant PrPsc is enriched in subcellular structures which contain the cation-independent mannose 6-phosphate receptor, ubiquitin-protein conjugates, beta-glucuronidase, and cathepsin B, termed late endosome-like organelles. The glycosylinositol phospholipid membrane-anchored PrPc will enter such compartment for normal degradation and the organelles may therefore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.
朊病毒脑病的特征是正常宿主基因产物PrPc的异常形式PrPsc在大脑中积累。目前尚不清楚PrPsc由PrPc形成的机制和位点。在本研究中，利用感染了ME7羊瘙痒病的小鼠脑，通过生化方法和双标记免疫金电子显微镜显示，蛋白酶K抗性PrPsc在含有不依赖阳离子的甘露糖6-磷酸受体、泛素-蛋白质缀合物、β-葡萄糖醛酸酶和组织蛋白酶B的亚细胞结构中富集，这些结构被称为晚期内体样细胞器。糖基磷脂酰肌醇膜锚定的PrPc会进入这样的区室进行正常降解，因此在这种羊瘙痒病小鼠模型中，这些细胞器可能充当将PrPc转化为传染性PrPsc的场所。
