Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation:: Nicotinic acetylcholine receptors, a case study
Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation:: Nicotinic acetylcholine receptors, a case study
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DOI：
10.1016/j.ijpara.2006.01.016
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发表时间：
2006-05-31
影响因子：
4
通讯作者：
Sattelle, D. B.
中科院分区：
文献类型：
--
作者：
Brown, L. A.;Jones, A. K.;Sattelle, D. B.
在1998年对自由生活的线虫--秀丽线虫的基因组进行完整测序之后，在许多基因的功能分配方面取得了快速的进展。正向遗传学和反向遗传学已被用于识别突触传递的新成分以及确定抗寄生虫药物靶点的关键成分。烟碱型乙酰胆碱受体(NAChRs)是典型的配体门控离子通道。这些跨膜蛋白的功能以及它们广泛的亚单位家族中不同成员的作用越来越被清楚地描述出来。线虫的简单神经系统拥有已知生物体中最大的烟碱型乙酰胆碱受体基因家族之一，结合遗传、基因芯片、生理和报告基因表达的研究大大加深了我们对线虫肌肉和神经元nAChR亚型组成的了解。化学到基因筛选已经确定了五个亚单位，它们是对抗寄生虫药左旋咪唑敏感的nAChRs的组成部分。在这些筛选中还发现了一个作用于左旋咪唑敏感的nAChR下游的新的、有效的靶点。对寄生线虫nAChRs的生理学和分子生物学研究也发现了左旋咪唑敏感和不敏感亚型，进一步的亚型正在调查中。(C)2006年澳大利亚寄生虫学协会，爱思唯尔有限公司出版。保留所有权利。
Following the complete sequencing of the genome of the free-living nematode, Caenorhabditis elegans, in 1998, rapid advances have been made in assigning functions to many genes. Forward and reverse genetics have been used to identify novel components of synaptic transmission as well as determine the key components of antiparasitic drug targets. The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels. The functions of these transmembrane proteins and the roles of the different members of their extensive subunit families are increasingly well characterised. The simple nervous system of C elegans possesses one of the largest nicotinic acetylcholine receptor gene families known for any organism and a combination of genetic, microarray, physiological and reporter gene expression studies have added greatly to our understanding of the components of nematode muscle and neuronal nAChR subtypes. Chemistry-to-gene screens have identified five subunits that are components of nAChRs sensitive to the antiparasitic drug, levamisole. A novel, validated target acting downstream of the levamisole-sensitive nAChR has also been identified in such screens. Physiology and molecular biology studies on nAChRs of parasitic nematodes have also identified levamisole-sensitive and insensitive subtypes and further subdivisions are under investigation. (c) 2006 Australian Society for Parasitology Inc Published by Elsevier Ltd. All rights reserved.