Redox-dependent structural ambivalence of the cytoplasmic domain in the inner ear-specific cadherin 23 isoform.
Redox-dependent structural ambivalence of the cytoplasmic domain in the inner ear-specific cadherin 23 isoform.
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DOI：
10.1016/j.bbrc.2007.11.102
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发表时间：
2008-02
影响因子：
3.1
通讯作者：
S. Yonezawa;A. Hanai;N. Mutoh;A. Moriyama;T. Kageyama
中科院分区：
文献类型：
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作者：
S. Yonezawa;A. Hanai;N. Mutoh;A. Moriyama;T. Kageyama
钙粘蛋白23（Cdh 23）是内耳机械电传导的重要因子，根据外显子68的存在和缺失，以两种选择性剪接形式存在，Cdh 23（+68）和Cdh 23（-68）。Cdh 23（+68）是内耳特有的。外显子68对应区域赋予胞质结构域（Cy）α-螺旋构型，并包含半胱氨酸残基Cys 3240。我们在这里证明，Cy（+68）以及跨膜（TM）加Cy（+68）区域在转染细胞中以两种不同的形式存在，还原型和非还原型，后者比前者以更紧凑的构型存在。Cys 3240 Ala取代完全消除了Cy（+68）的观察特征。用马来酸二乙酯（一种谷胱甘肽消耗试剂）处理TMCy（+68）转染的细胞，导致TMCy（+68）的非还原形式转化为还原形式，表明谷胱甘肽是Cys 3240结合伴侣。哺乳动物Cdh 23 Cy序列的多重比对表明，哺乳动物Cdh 23 Cy中存在构象诱导型Cys，但低等脊椎动物没有。Cys依赖的结构矛盾的Cdh 23在内耳机械感觉的影响进行了讨论。
Cadherin 23 (Cdh23), an essential factor in inner ear mechano-electric transduction, exists in two alternatively spliced forms, Cdh23(+68) and Cdh23(−68), depending on the presence and absence of exon 68. Cdh23(+68) is inner ear-specific. The exon 68-corresponding region confers an α-helical configuration upon the cytoplasmic domain (Cy) and includes a cysteine residue, Cys3240. We demonstrate here that Cy(+68) as well as the transmembrane (TM) plus Cy(+68) region is present in two different forms in transfected cells, reduced and non-reduced, the latter existing in more compact configuration than the former. The observed characteristic of Cy(+68) was completely abolished by Cys3240Ala substitution. Treatment of TMCy(+68)-transfected cells with diethyl maleate, a glutathione depleting reagent, resulted in conversion of the non-reduced to the reduced form of TMCy(+68), suggesting glutathione to be a Cys3240-binding partner. Multiple alignment of mammalian Cdh23Cy sequences indicated the occurrence of conformation-inducible Cys in Cdh23Cy of mammals, but not lower vertebrates. The implications of Cys-dependent structural ambivalence of Cdh23 in inner ear mechanosensation are discussed.