Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors
Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour and are functional orthologues of Haemonchus contortus receptors
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DOI：
10.1016/j.molbiopara.2006.02.003
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发表时间：
2006-05-01
影响因子：
1.5
通讯作者：
Wolstenholme, A
中科院分区：
文献类型：
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作者：
Cook, A;Aptel, N;Wolstenholme, A
伊维菌素驱虫作用的靶位点是线虫谷氨酸门控氯离子通道α亚基（GluCl α）家族，其以高亲和力结合药物并介导其强效麻痹作用。虽然伊维菌素对线虫咽肌的作用相对较好理解，但其对运动活动的影响尚不清楚。在这里，我们使用RNAi和基因敲除表明，四个GluCla亚基参与调节秀丽隐杆线虫的运动活动模式。这些亚基的捻转血矛线虫直向同源物HcGluCL α 3已被证明在运动神经系统中表达，在这里，我们已经证明它是一个功能性的，以及结构，直向同源物，凭借观察，它可以恢复C.当在avr-14启动子的控制下表达时，elegans GluCl α突变体avr-14（ad 1032）。这支持了伊维菌素通过激活运动神经系统中的GluCl通道对寄生线虫发挥麻痹作用的论点。此外，C. elegans提供了一种方法来进一步理解这类重要的驱虫靶标。(c)2006 Elsevier B. V.保留所有权利。
The target site for the anthelmintic action of ivermectin is a family of nematode glutamate-gated chloride channel alpha subunits (GluCl alpha) that bind the drug with high affinity and mediate its potent paralytic action. Whilst the action of ivermectin on the pharyngeal muscle of nematodes is relatively well understood, its effect on locomotor activity is less clear. Here we use RNAi and gene knockouts to show that four GluCla subunits are involved in regulating the pattern of locomotor activity in Caenorhabditis elegans. A Haemonchus contortus orthologue of these subunits, HcGluCL alpha 3, has been shown to be expressed in the motor nervous system and here we have shown that it is a functional, as well as a structural, orthologue by virtue of the observation that it can restore normal motor movement in the C. elegans GluCl alpha mutant, avr-14(ad1032), when expressed under the control of the avr-14 promoter. This supports the contention that ivermectin exerts its paralytic action on parasitic nematodes through activation of GluCl channels in the motor nervous system. Furthermore, functional complementation in C. elegans provides a method to further the understanding of this important class of anthelmintic targets. (c) 2006 Elsevier B.V. All rights reserved.