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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Diversifying the repertoire of G protein-coupled receptors through oligomerization
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Diversifying the repertoire of G protein-coupled receptors through oligomerization

机译：通过寡聚化使G蛋白偶联受体的组成多样化

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Oligomerization of G protein-coupled receptors (GPCRs) has received much attention over the past several years (1, 2). The consequences arising from oligo-meric arrangements of GPCRs are proposed to play a central role in signal transduction (3). Except for a few cases (e.g., refs. 4-6), many of the recent studies investigating GPCR oligomerization have involved heterologous expression systems of native and modified receptors (7). The studies by Waldhoer et al. in this issue of PNAS (8) broaden the previous work by placing it in a physiologically relevant context. The opioid receptors studied by Waldhoer et al. (8) belong to the GPCR su-perfamily and exist as three types: δ, κ, and μ,. All three types have been shown previously to form homooligomers individually and heterooligomers with each other (5, 9-12). Waldhoer et al. demonstrate the existence of a functional het-eromer of δ and κ opioid receptors in vivo that localizes specifically in the spinal cord. This study gives credence to the wealth of evidence for GPCR oligomerization in vitro. The δ-κ hetero-mer has a novel pharmacology and is activated by the heteromer-specific agonist 6'-guanidinonaltrindole (6′-GNTI) (Fig. 1), which illustrates the added diversity offered by heterooligomerization (Fig. 2). The novel pharmacological profile of the δ-κ heteromer and the availability of ligands that are specific to this heterooligomer (13, 14) open the door to more selectively targeted therapeutics with reduced side effects.
机译：在过去的几年中，G蛋白偶联受体（GPCR）的寡聚化受到了广泛关注（1、2）。有人提出，由GPCR的寡聚安排引起的后果在信号转导中起着核心作用（3）。除少数情况外（例如参考文献4-6），许多研究GPCR寡聚化的最新研究都涉及天然和修饰受体的异源表达系统（7）。 Waldhoer等人的研究。在本期PNAS（8）中，通过将其置于生理相关的环境中来扩大了以前的工作。 Waldhoer等人研究了阿片受体。 （8）属于GPCR超家族，以δ，κ和μi三种类型存在。先前已显示所有这三种类型可分别形成均聚物和彼此形成杂聚物（5、9-12）。 Waldhoer等。证明了体内存在δ和κ阿片样物质受体的功能性异聚体，其特异性地定位在脊髓中。这项研究为体外GPCR寡聚的大量证据提供了可信度。 δ-κ异源单体具有新颖的药理作用，并被异源单体特异性激动剂6'-胍基纳丁三醇（6'-GNTI）激活（图1），这说明了杂聚所带来的额外多样性（图2）。 δ-κ异源异构体的新药理学特征以及对该异源寡聚体具有特异性的配体（13，14）的可用性为更具选择性，副作用减少的靶向治疗打开了大门。

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