A PRION-LIKE PROTEIN FROM CHICKEN BRAIN COPURIFIES WITH AN ACETYLCHOLINE RECEPTOR-INDUCING ACTIVITY
A PRION-LIKE PROTEIN FROM CHICKEN BRAIN COPURIFIES WITH AN ACETYLCHOLINE RECEPTOR-INDUCING ACTIVITY
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DOI：
10.1073/pnas.88.17.7664
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发表时间：
1991-09-01
影响因子：
11.1
通讯作者：
FISCHBACH, GD
中科院分区：
文献类型：
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作者：
HARRIS, DA;FALLS, DL;FISCHBACH, GD
哺乳动物朊病毒蛋白（PrP（C））是一种功能未知的细胞蛋白，其改变的同种型（PrP（Sc））是感染性颗粒（朊病毒）的组分，被认为是导致人类和动物海绵状脑病的原因。我们在这里报告的cDNA的分离，编码的鸡蛋白，是同源的PrP（C）。这种鸡朊病毒样蛋白（ch-PrLP）与小鼠PrP在33%的氨基酸位置相同，包括24个相同残基的不间断延伸，并且它显示出相同的结构域。此外，ch-PrLP与其哺乳动物对应物一样，通过糖基磷脂酰肌醇锚附着于细胞表面。我们认为，ch-PrLP是乙酰胆碱受体诱导活性制剂中的主要蛋白质，基于其刺激培养的肌管合成烟碱受体的能力，已从脑中纯化> 10（6）倍。ch-PrLP基因早在胚胎第6天就在脊髓和大脑中表达;在脊髓中，该蛋白质似乎集中在运动神经元中。因此，我们的研究结果提出了朊病毒蛋白正常调节神经肌肉接头化学感受器数量的可能性，也许在中枢神经系统也是如此。
The mammalian prion protein (PrP(C)) is a cellular protein of unknown function, an altered isoform of which (PrP(Sc)) is a component of the infectious particle (prion) thought to be responsible for spongiform encephalopathies in humans and animals. We report here the isolation of a cDNA that encodes a chicken protein that is homologous to PrP(C). This chicken prion-like protein (ch-PrLP) is identical to the mouse PrP at 33% of its amino acid positions, including an uninterrupted stretch of 24 identical residues, and it displays the same structural domains. In addition, ch-PrLP, like its mammalian counterpart, is attached to the cell surface by a glycosylphosphatidylinositol anchor. We rind that ch-PrLP is the major protein in preparations of an acetylcholine receptor-inducing activity that has been purified > 10(6)-fold from brain on the basis of its ability to stimulate synthesis of nicotinic receptors by cultured myotubes. The ch-PrLP gene is expressed in the spinal cord and brain as early as embryonic day 6; and in the spinal cord, the protein appears to be concentrated in motor neurons. Our results therefore raise the possibility that prion proteins serve normally to regulate the chemoreceptor number at the neuromuscular junction and perhaps in the central nervous system as well.