Identification of RL-TGR, a coreceptor involved in aversive chemical signaling
Identification of RL-TGR, a coreceptor involved in aversive chemical signaling
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DOI：
10.1073/pnas.1000343107
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发表时间：
2010-07-06
影响因子：
11.1
通讯作者：
McCarty, Nael A.
中科院分区：
文献类型：
--
作者：
Cohen, Staci P.;Haack, Karla K. V.;McCarty, Nael A.
化学信号在捕食者-猎物相互作用和摄食动力学中起着重要作用。像其他固着或缓慢移动的生物一样，一些海绵含有令人厌恶的化合物，可以保护这些生物免受捕食。我们试图确定和表征的鱼类化学感受器，检测这些化合物之一。使用表达克隆在非洲爪蟾卵母细胞共表达囊性纤维化跨膜传导调节（CFTR）氯离子通道，β-2肾上腺素能受体（β（2）AR），和组分的斑马鱼cDNA文库，我们分离的cDNA克隆编码受体活性修饰蛋白（RAMP）样三萜苷受体（RL-TGR），一种新的辅助受体参与信号响应三萜苷。这种辅助受体似乎在结构上和功能上与RAMP相关，RAMP是一个辅助受体家族，其与G蛋白偶联受体（GPCR）物理相关并改变其活性。在来自福莫苷反应性卵母细胞的膜中，RL-TGR与β（2）AR以明显的复合物免疫沉淀。在HEK 293细胞中，β（2）AR的共表达诱导RL-TGR从细胞质运输到质膜。这些结果表明，RL-TGR在捕食性鱼类与β（2）AR或另一种生理上更相关的GPCR物理关联，并修改其药理学，以响应海绵中发现的三萜糖苷，作为鱼类的潜在食物来源。RL-TGR形成了一种辅助受体，对海洋环境中的化学防御化合物做出反应，它的发现可能会导致识别介导化学防御信号的其他受体。
Chemical signaling plays an important role in predator-prey interactions and feeding dynamics. Like other organisms that are sessile or slow moving, some marine sponges contain aversive compounds that defend these organisms from predation. We sought to identify and characterize a fish chemoreceptor that detects one of these compounds. Using expression cloning in Xenopus oocytes coexpressing the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, the beta-2 adrenergic receptor (beta(2)AR), and fractions of a zebrafish cDNA library, we isolated a cDNA clone encoding receptor activity-modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), a novel coreceptor involved in signaling in response to triterpene glycosides. This coreceptor appears to be structurally and functionally related to RAMPs, a family of coreceptors that physically associate with and modify the activity of G protein-coupled receptors (GPCRs). In membranes from formoside-responsive oocytes, RL-TGR was immunoprecipitated in an apparent complex with beta(2)AR. In HEK293 cells, coexpression of beta(2)AR induced the trafficking of RL-TGR from the cytoplasm to the plasma membrane. These results suggest that RL-TGR in the predatory fish physically associates with the beta(2)AR or another, more physiologically relevant GPCR and modifies its pharmacology to respond to triterpene glycosides found in sponges that serve as a potential food source for the fish. RL-TGR forms a coreceptor that responds to a chemical defense compound in the marine environment, and its discovery might lead the way to the identification of other receptors that mediate chemical defense signaling.