Jones Andrew K, Sattelle David B
MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX.
Bioessays. 2004 Jan;26(1):39-49. doi: 10.1002/bies.10377.
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that bring about a diversity of fast synaptic actions. Analysis of the Caenorhabditis elegans genome has revealed one of the most-extensive and diverse nAChR gene families known, consisting of at least 27 subunits. Striking variation with possible functional implications has been observed in normally conserved motifs at the acetylcholine-binding site and in the channel-lining region. Some nAChR subunits are particular to neurons whilst others are present in both neurons and muscles. The localization of subunits in non-synaptic regions suggests novel roles for nAChRs. Genetic and heterologous expression studies have identified a subset of nAChR subunits that are important drug targets while the study of mutants has identified genes functionally-linked to nAChRs. Future studies using C. elegans offer the prospect of increasing our understanding of the functional diversity of a complex nAChR gene family as well as addressing the role of nAChRs and associated proteins in human disorders.
烟碱型乙酰胆碱受体(nAChRs)是配体门控离子通道,可引发多种快速突触作用。对秀丽隐杆线虫基因组的分析揭示了已知最为广泛和多样的nAChR基因家族之一,该家族由至少27个亚基组成。在乙酰胆碱结合位点和通道内衬区域的正常保守基序中观察到了具有可能功能意义的显著变异。一些nAChR亚基是神经元特有的,而其他亚基则同时存在于神经元和肌肉中。亚基在非突触区域的定位表明nAChRs具有新的作用。遗传和异源表达研究已经确定了一部分作为重要药物靶点的nAChR亚基,而对突变体的研究则确定了与nAChRs功能相关的基因。未来使用秀丽隐杆线虫的研究有望增进我们对复杂nAChR基因家族功能多样性的理解,并阐明nAChRs及相关蛋白在人类疾病中的作用。