RTP family members induce functional expression of mammalian odorant receptors
RTP family members induce functional expression of mammalian odorant receptors
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DOI：
10.1016/j.cell.2004.11.021
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发表时间：
2004-11-24
期刊：
影响因子：
64.5
通讯作者：
Matsunami, H
中科院分区：
文献类型：
--
作者：
Saito, H;Kubota, M;Matsunami, H
G蛋白偶联受体（GPCR）转运至细胞表面膜对于受体识别其配体至关重要。然而，哺乳动物GPCR气味受体（OR）当在细胞中异源表达时，在细胞表面上表达很差。在这里，我们表明，跨膜蛋白RTP1和RTP2促进HEK293T细胞中表达的OR的功能性细胞表面表达。编码这些蛋白质的基因在嗅觉神经元中特异性表达。这些蛋白质与OR蛋白相关，并增强对气味的OR反应。第三种蛋白质REEP 1也有类似的作用，尽管作用较弱。这些发现表明，RTP1和RTP2特别是发挥重要作用，在易位的OR到质膜，以及在功能的OR。我们已经使用这种方法来确定活性气味配体的OR，提供了一个平台，筛选大OR家族的化学选择性。
Transport of G protein-coupled receptors (GPCRs) to the cell surface membrane is critical in order for the receptors to recognize their ligands. However, mammalian GPCR odorant receptors (ORs), when heterologously expressed in cells, are poorly expressed on the cell surface. Here we show that the transmembrane proteins RTP1 and RTP2 promote functional cell surface expression of ORs expressed in HEK293T cells. Genes encoding these proteins are expressed specifically in olfactory neurons. These proteins are associated with OR proteins and enhance the OR responses to odorants. Similar although weaker effects were seen with a third protein, REEP1. These findings suggest that RTP1 and RTP2 in particular play significant roles in the translocation of ORs to the plasma membrane as well as in the functioning of ORs. We have used this approach to identify active odorant ligands for ORs, providing a platform for screening the chemical selectivity of the large OR family.