Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity
Neuroligin-deficient mutants of C. elegans have sensory processing deficits and are hypersensitive to oxidative stress and mercury toxicity
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DOI：
10.1242/dmm.003442
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发表时间：
2010-05-01
影响因子：
4.3
通讯作者：
Rand, James B.
中科院分区：
文献类型：
--
作者：
Hunter, Jerrod W.;Mullen, Gregory P.;Rand, James B.
神经胶蛋白是突触后细胞粘附蛋白，其特异性结合称为神经毒素的突触前膜蛋白。人类神经连接素基因的突变与某些家族中的自闭症谱系障碍有关。秀丽隐杆线虫只有一个神经连接素基因（nlg-1），大约是C.包括一些感觉神经元、中间神经元和胆碱能运动神经元的子集在内的线虫神经元表达神经配蛋白转录报道子。C.秀丽线虫是可以存活的，它们在任何主要的运动功能上都没有缺陷。然而，神经连接素突变体在感觉行为和感觉处理的子集中是有缺陷的，并且对氧化应激和汞化合物过敏;行为缺陷与经常与自闭症谱系障碍相关的特征惊人地相似。我们的研究结果表明，在自闭症谱系障碍的发展中，突触形成或功能的遗传缺陷与对环境因素的敏感性之间可能存在联系。
Neuroligins are postsynaptic cell adhesion proteins that bind specifically to presynaptic membrane proteins called neurexins. Mutations in human neuroligin genes are associated with autism spectrum disorders in some families. The nematode Caenorhabditis elegans has a single neuroligin gene (nlg-1), and approximately a sixth of C. elegans neurons, including some sensory neurons, interneurons and a subset of cholinergic motor neurons, express a neuroligin transcriptional reporter. Neuroligin-deficient mutants of C. elegans are viable, and they do not appear deficient in any major motor functions. However, neuroligin mutants are defective in a subset of sensory behaviors and sensory processing, and are hypersensitive to oxidative stress and mercury compounds; the behavioral deficits are strikingly similar to traits frequently associated with autism spectrum disorders. Our results suggest a possible link between genetic defects in synapse formation or function, and sensitivity to environmental factors in the development of autism spectrum disorders.