Unique expression of connexins in the human cochlea
Unique expression of connexins in the human cochlea
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DOI：
10.1016/j.heares.2009.01.010
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发表时间：
2009-04-01
期刊：
影响因子：
2.8
通讯作者：
Rask-Andersen, Helge
中科院分区：
文献类型：
--
作者：
Liu, Wei;Bostrom, Marja;Rask-Andersen, Helge
编码连接蛋白26(Cx26)和连接蛋白30(Cx30)的基因GJB2和GJB6的突变被认为与人类的非综合征性语前聋有关。这些蛋白质可能形成所谓的缝隙连接(GJ)或细胞间的跨细胞通路。由于GJ连接蛋白突变导致的耳聋的发病机制尚不清楚，部分原因是在人类耳朵上进行的检查很少。在此，我们分析了Cx26和Cx30在5个新鲜的正常人耳蜗中的表达和分布。脱钙标本的免疫组织化学(包括共聚焦显微镜)显示，这些蛋白在人类耳蜗组织中广泛表达。在侧壁，Cx26和Cx30有很强的抗体共标记，支持含有异构体Cx26/Cx30连接子的通道的存在。在Corti器官的支持细胞区有一些共标记，主要包括Claudius细胞和Deiter细胞，除了在同一区域有单独的Cx26和Cx30标记外，提示既有同源/同型模式，也有杂交型(异型或异型)。Cx30、Cx26和Cx36也与螺旋神经节I型神经元相关，后者是神经元特有的缝隙连接蛋白。除了蝙蝠外，基于缝隙连接的电突触在哺乳动物的听觉系统中并不存在，在蝙蝠中，它们可能在快速的电神经传递中发挥作用，有助于回声定位。讨论了它们在人类听神经信号处理中的潜在作用，以及连接蛋白在人类耳蜗组织中的非GJ作用。(C)2009爱思唯尔B.V.保留所有权利。
Mutations in the genes GJB2 and GJB6, which encode the proteins Connexin 26 (Cx26) and Connexin 30 (Cx30), have been linked to nonsyndromic prelingual deafness in humans. These proteins may form so-called gap junctions (GJ) or transcellular pathways between cells. The pathogenesis of deafness due to GJ Connexin mutations remains unclear partly because examinations performed in the human ear are infrequent. Here we analysed the expression and distribution of Cx26 and Cx30 in five fresh normal human cochleae taken out at occasional surgery. Immunohistochemistry including confocal microscopy in decalcified specimen showed that these proteins are widely expressed in the human cochlea. In the lateral wall there was strong antibody co-labeling for Cx26 and Cx30 that support the existence of channels comprising heteromeric Cx26/Cx30 connexons. In the organ of Corti there were some co-labeling in the supporting cell area including mainly the Claudius cells and Deiter cells of these two Cxs, apart from isolated Cx26 and Cx30 labeling in the same area, suggestive of both homomeric/homotypic pattern and hybrid pattern (heteromeric or heterotypic). Cx30, Cx26 and Connexin 36 (Cx36) immunoreactivity was also associated with spiral ganglion type I neurons, the latter being a gap junction protein specific to neurons. Gap-junction-based electrical synapses are not known to occur in mammalian auditory system other than in bats where they may play a role for fast electrical nerve transmission useful for echolocation. Their potential role in the processing of human auditory nerve signaling as well as non-GJ roles of the connexins in human cochlea is discussed. (c) 2009 Elsevier B.V. All rights reserved.