Department of Biology, Queen's University Kingston, ON, Canada.
Front Endocrinol (Lausanne). 2012 Aug 9;3:93. doi: 10.3389/fendo.2012.00093. eCollection 2012.
The G-protein coupled receptor (GPCR) family is comprised of seven transmembrane domain proteins and play important roles in nerve transmission, locomotion, proliferation and development, sensory perception, metabolism, and neuromodulation. GPCR research has been targeted by drug developers as a consequence of the wide variety of critical physiological functions regulated by this protein family. Neuropeptide GPCRs are the least characterized of the GPCR family as genetic systems to characterize their functions have lagged behind GPCR gene discovery. Drosophila melanogaster and Caenorhabditis elegans are genetic model organisms that have proved useful in characterizing neuropeptide GPCRs. The strength of a genetic approach leads to an appreciation of the behavioral plasticity that can result from subtle alterations in GPCRs or regulatory proteins in the pathways that GPCRs control. Many of these invertebrate neuropeptides, GPCRs, and signaling pathway components serve as models for mammalian counterparts as they have conserved sequences and function. This review provides an overview of the methods to match neuropeptides to their cognate receptor and a state of the art account of neuropeptide GPCRs that have been characterized in D. melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation.
G 蛋白偶联受体(GPCR)家族由七个跨膜域蛋白组成,在神经传递、运动、增殖和发育、感觉感知、代谢和神经调节中发挥重要作用。由于该蛋白家族调节的各种关键生理功能,GPCR 研究一直是药物开发者的目标。神经肽 GPCR 是 GPCR 家族中特征最不明显的,因为用于描述其功能的遗传系统落后于 GPCR 基因的发现。黑腹果蝇和秀丽隐杆线虫是遗传模式生物,它们在鉴定神经肽 GPCR 方面非常有用。遗传方法的优势在于可以认识到 GPCR 或 GPCR 控制的途径中的调节蛋白的微小改变可能导致的行为可塑性。许多这些无脊椎动物神经肽、GPCR 和信号转导途径成分作为哺乳动物对应物的模型,因为它们具有保守的序列和功能。本综述提供了一种将神经肽与其同源受体匹配的方法概述,以及在黑腹果蝇和秀丽隐杆线虫中鉴定的神经肽 GPCR 及其通过遗传操作揭示的行为的最新描述。