Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (Cx26 and Cx30), impair the formation of membrane channels and cause autosomal syndromic and non-syndromic hearing loss. In cochlear non-sensory supporting cells, Cx26 and Cx30 form two types of homomeric and heteromeric gap junctions. The biogenesis processes of these channels occurring in situ remain largely unknown. Here we show that Cx30 homomeric and Cx26/Cx30 heteromeric gap junctions exhibit distinct assembly mechanisms in the cochlea. When expressed as homomeric channels, Cx30 preferentially interacts with β-actin in the peripheral non-junctional membrane region, called perinexus, and strongly relies on the actin network for gap junction plaque assembly. In contrast, we found that Cx26/Cx30 heteromeric gap junction plaques are devoid of perinexus and associated actin network, and resist to actin-depolymerizating drug. This supports that Cx26/Cx30 oligomers could be directly delivered from the interior of the cell to the junctional plaque. Altogether, our data provide a novel insight in homomeric and heteromeric gap junction plaque assembly in the cochlea.

中文翻译：

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耳蜗连接蛋白 30 同聚和异聚通道表现出不同的组装机制

编码连接蛋白 26 和 30（Cx26 和 Cx30）的 GJB2 和 GJB6 中的许多突变会损害膜通道的形成并导致常染色体综合征和非综合征听力损失。在耳蜗非感觉支持细胞中，Cx26 和 Cx30 形成两种类型的同聚和异聚间隙连接。原位发生的这些通道的生物发生过程在很大程度上仍然未知。在这里，我们显示 Cx30 同源和 Cx26/Cx30 异聚间隙连接在耳蜗中表现出不同的组装机制。当表达为同源通道时，Cx30 优先与外周非连接膜区域中的 β-肌动蛋白相互作用，称为外周，并强烈依赖肌动蛋白网络进行间隙连接斑块组装。相比之下，我们发现 Cx26/Cx30 异聚间隙连接斑块没有 perinexus 和相关的肌动蛋白网络，并且对肌动蛋白解聚药物具有抵抗力。这支持 Cx26/Cx30 寡聚体可以直接从细胞内部传递到连接斑块。总而言之，我们的数据提供了耳蜗中同聚和异聚间隙连接斑块组装的新见解。