The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein
The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein
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DOI：
10.1093/emboj/20.21.5863
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发表时间：
2001-11-01
期刊：
影响因子：
11.4
通讯作者：
Weiss, S
中科院分区：
文献类型：
--
作者：
Gauczynski, S;Peyrin, JM;Weiss, S
最近，我们确定了37 kDa层粘连蛋白受体前体（LRP）作为朊病毒蛋白（PrP）的相互作用。在这里，我们显示存在的37-kDa的LRP和其成熟的67-kDa的形式被称为高亲和力层粘连蛋白受体（LR）在质膜部分的N2 a细胞，而只有37-kDa的LRP检测到在婴儿仓鼠肾（BHK）细胞。PrP与LRP/LR共定位于N2 a细胞和Semliki Forest病毒（SFV）RNA转染的BHK细胞的表面上。细胞结合试验揭示了LRP/LR依赖性结合的细胞PrP的神经元和非神经元细胞。LRP在BHK细胞表面的过表达导致外源性PrP的结合。PrP+/+和PrP 0/0原代神经元中的细胞结合相似，表明PrP不作为LRP/LR的共受体。LRP/LR依赖的PrP内化在4 ℃时被阻断。从BHK细胞分泌缺乏跨膜结构域（aa 86-101）的LRP突变体废除PrP结合和内化。我们的研究结果表明，LRP/LR作为哺乳动物细胞表面的细胞PrP的受体。
Recently, we identified the 37-kDa laminin receptor precursor (LRP) as an interactor for the prion protein (PrP). Here, we show the presence of the 37-kDa LRP and its mature 67-kDa form termed high-affinity laminin receptor (LR) in plasma membrane fractions of N2a cells, whereas only the 37-kDa LRP was detected in baby hamster kidney (BHK) cells. PrP co-localizes with LRP/LR on the surface of N2a cells and Semliki Forest virus (SFV) RNA transfected BHK cells. Cell-binding assays reveal the LRP/LR-dependent binding of cellular PrP by neuronal and non-neuronal cells. Hyperexpression of LRP on the surface of BHK cells results in the binding of exogenous PrP. Cell binding is similar in PrP+/+ and PrP0/0 primary neurons, demonstrating that PrP does not act as a co-receptor of LRP/LR. LRP/LR-dependent internalization of PrP is blocked at 4 degreesC. Secretion of an LRP mutant lacking the transmembrane domain (aa 86-101) from BHK cells abolishes PrP binding and internalization. Our results show that LRP/LR acts as the receptor for cellular PrP on the surface of mammalian cells.