Hegde R S, Mastrianni J A, Scott M R, DeFea K A, Tremblay P, Torchia M, DeArmond S J, Prusiner S B, Lingappa V R
Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
Science. 1998 Feb 6;279(5352):827-34. doi: 10.1126/science.279.5352.827.
At the endoplasmic reticulum membrane, the prion protein (PrP) can be synthesized in several topological forms. The role of these different forms was explored with transgenic mice expressing PrP mutations that alter the relative ratios of the topological forms. Expression of a particular transmembrane form (termed CtmPrP) produced neurodegenerative changes in mice similar to those of some genetic prion diseases. Brains from these mice contained CtmPrP but not PrPSc, the PrP isoform responsible for transmission of prion diseases. Furthermore, in one heritable prion disease of humans, brain tissue contained CtmPrP but not PrPSc. Thus, aberrant regulation of protein biogenesis and topology at the endoplasmic reticulum can result in neurodegeneration.
在内质网膜上，朊病毒蛋白（PrP）可以以多种拓扑形式合成。通过表达改变拓扑形式相对比例的PrP突变体的转基因小鼠，对这些不同形式的作用进行了探索。一种特定跨膜形式（称为CtmPrP）的表达在小鼠中产生了类似于某些遗传性朊病毒疾病的神经退行性变化。这些小鼠的大脑含有CtmPrP，但不含有PrPSc，PrPSc是负责朊病毒疾病传播的PrP异构体。此外，在人类的一种遗传性朊病毒疾病中，脑组织含有CtmPrP，但不含有PrPSc。因此，内质网处蛋白质生物合成和拓扑结构的异常调节可导致神经退行性变。
