Functional genomics, the search for novel neurotransmitters and neuropeptides
Functional genomics, the search for novel neurotransmitters and neuropeptides
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DOI：
10.1016/s0014-5793(98)00524-9
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发表时间：
1998-06-23
期刊：
影响因子：
3.5
通讯作者：
Civelli, O
中科院分区：
文献类型：
--
作者：
Civelli, O
功能基因组学可以被定义为寻找一个基因的生理作用，只有它的主要序列是已知的。大多数编码含有7个疏水片段的蛋白质的基因编码G蛋白偶联受体（GPCR），尽管其中许多已被证明与已知的天然配体相互作用，但一些结合配体迄今尚未分离。作为功能基因组学的一个例子，已经开发了一种“孤儿受体策略”来鉴定孤儿GPCR的天然配体。这一策略的应用必将彻底改变我们对调节突触传递的初级信使的多样性的理解。本文讨论了孤儿受体策略的基本概念和一些特殊问题。该策略的潜力体现在其成功中，最终发现了神经肽“食欲素FQ/伤害感受素”和“食欲素/下丘脑泌素”。导致这些神经肽的表征的步骤进行了讨论，是一些进一步的研究，已经解决了这些神经肽的作用。最后，一些孤儿受体策略的应用的影响进行了讨论。(C)1998年欧洲生物化学学会联合会。
Functional genomics can be defined as the search for the physiological role of a gene for which only its primary sequence is known. Most of the genes encoding proteins containing seven hydrophobic stretches code for G protein-coupled receptors (GPCRs), Although many of these have been shown to interact with known natural ligands, several bind ligands,which have not been thus far isolated. These are the so-called orphan GPCRs, As an example of functional genomics, an 'orphan receptor strategy' has been del eloped to identify the natural ligands of orphan GPCRs. The application of this strategy is bound to revolutionize our understanding of the diversity of the primary messengers which modulate synaptic transmission, This review discusses the basic concepts and some of the particular problems associated with the orphan receptor strategy. The strategy's potential is exemplified by its successes which culminated in the discovery of the neuropeptides 'orphanin FQ/nociceptin' and 'orexins/hypocretins'. The steps that led to the characterization of these neuropeptides are discussed as are some of the further studies that have addressed the roles of these neuropeptides. To conclude, some of the implications of the application of the orphan receptor strategy are discussed. (C) 1998 Federation of European Biochemical Societies.