Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death

doi:10.1371/journal.pone.0074732

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	Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death
	Ren, Q; Riquelme, MA; Xu, J; Yan, X; Nicholson, BJ; Gu, SM; Jiang, JX; Jiang, JX (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
刊名	PLOS ONE
	2013-09-03
卷号	8 期号:9 页码:-
ISSN号	1932-6203
DOI	10.1371/journal.pone.0074732
文献子类	Article
英文摘要	Connexin channels play a critical role in maintaining metabolic homeostasis and transparency of the lens. Mutations in connexin genes are linked to congenital cataracts in humans. The G143R missense mutation on connexin (Cx) 46 was recently reported to be associated with congenital Coppock cataracts. Here, we showed that the G143R mutation decreased Cx46 gap junctional coupling in a dominant negative manner; however, it significantly increased gap junctional plaques. The G143R mutant also increased hemichannel activity, inversely correlated with the level of Cx46 protein on the cell surface. The interaction between cytoplasmic loop domain and C-terminus has been shown to be involved in gating of connexin channels. Interestingly, the G143R mutation enhanced the interaction between intracellular loop and Cx46. Furthermore, this mutation decreased cell viability and the resistance of the cells to oxidative stress, primarily due to the increased hemichannel function. Together, these results suggest that mutation of this highly conserved residue on the cytoplasmic loop domain of Cx46 enhances its interaction with the C-terminus, resulting in a reduction of gap junction channel function, but increased hemichannel function. This combination leads to the development of human congenital cataracts.
学科主题	Science & Technology - Other Topics
出版地	SAN FRANCISCO
资助项目	美国国立卫生研究院项目
项目编号	Institutes of Health [EY012085] ; Welch Foundation [AQ-1507]
语种	英语
WOS记录号	WOS:000324338200121
资助机构	NIH
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/125806]
专题	第一临床医学院_期刊论文
通讯作者	Jiang, JX (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
推荐引用方式 GB/T 7714	Ren, Q,Riquelme, MA,Xu, J,et al. Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death[J]. PLOS ONE,2013,8(9):-.
APA	Ren, Q.,Riquelme, MA.,Xu, J.,Yan, X.,Nicholson, BJ.,...&Jiang, JX .(2013).Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death.PLOS ONE,8(9),-.
MLA	Ren, Q,et al."Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death".PLOS ONE 8.9(2013):-.