Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human alpha 7 Nicotinic Receptor

	Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human alpha 7 Nicotinic Receptor
	Zhang, Qinhui; Du, Yingjie; Zhang, Jianliang; Xu, Xiaojun; Xue, Fenqin; Guo, Cong; Huang, Yao; Lukas, Ronald J.; Chang, Yongchang
刊名	PLOS ONE
	2015
卷号	10 期号:9 页码:-
关键词	CHOLINERGIC ANTIINFLAMMATORY PATHWAY POSITIVE ALLOSTERIC MODULATION GATED ION-CHANNEL ACETYLCHOLINE-RECEPTOR AGONIST-BINDING INTERNATIONAL UNION TRANSMEMBRANE SITE SILENT AGONIST AMINO-ACIDS ACTIVATION
通讯作者	Chang, YC (reprint author), St Josephs Hosp, Barrow Neurol Inst, Div Neurobiol, Phoenix, AZ 85013 USA.
产权排序	2
合作状况	国际
英文摘要	The alpha 7nicotinic receptor (nAChR) is a major subtype of the nAChRs in the central nervous system, and the receptor plays an important role in brain function. In the dbSNP database, there are 55 single nucleotide polymorphisms (SNPs) that cause missense mutations of the human alpha 7nAChR in the coding region. In this study, we tested the impact of 14 SNPs that cause missense mutations in the agonist binding site or the coupling region between binding site and channel gate on the receptor function. The wild type or mutant receptors were expressed or co-expressed in Xenopus oocytes, and the agonist-induced currents were tested using two-electrode voltage clamp. Our results demonstrated that 6 mutants were nonfunctional, 4 mutants had reduced current expression, and 1 mutants altered ACh and nicotine efficacy in the opposite direction, and one additional mutant had slightly reduced agonist sensitivity. Interestingly, the function of most of these nonfunctional mutants could be rescued by a7nAChR positive allosteric modulator PNU-120596 and agonist-PAM 4BP-TQS. Finally, when coexpressed with the wild type, the nonfunctional mutants could also influence the receptor function. These changes of the receptor properties by the mutations could potentially have an impact on the physiological function of the alpha 7nAChR-mediated cholinergic synaptic transmission and anti-inflammatory effects in the human SNP carriers. Rescuing the nonfunctional mutants could provide a novel way to treat the related disorders.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
语种	英语
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/27570]
专题	成都生物研究所_天然产物研究
推荐引用方式 GB/T 7714	Zhang, Qinhui,Du, Yingjie,Zhang, Jianliang,et al. Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human alpha 7 Nicotinic Receptor[J]. PLOS ONE,2015,10(9):-.
APA	Zhang, Qinhui.,Du, Yingjie.,Zhang, Jianliang.,Xu, Xiaojun.,Xue, Fenqin.,...&Chang, Yongchang.(2015).Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human alpha 7 Nicotinic Receptor.PLOS ONE,10(9),-.
MLA	Zhang, Qinhui,et al."Functional Impact of 14 Single Nucleotide Polymorphisms Causing Missense Mutations of Human alpha 7 Nicotinic Receptor".PLOS ONE 10.9(2015):-.