Molecular basis of gap junctional communication in the CNS of the leech Hirudo medicinalis
Molecular basis of gap junctional communication in the CNS of the leech Hirudo medicinalis
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DOI：
10.1523/jneurosci.3676-03.2004
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发表时间：
2004-01-28
影响因子：
5.3
通讯作者：
Davies, JA
中科院分区：
文献类型：
--
作者：
Dykes, IM;Freeman, FM;Davies, JA
间隙连接是细胞间的通道，允许离子和小分子在细胞之间通过。在神经系统中，缝隙连接介导神经元之间的电耦合。尽管共享一个共同的拓扑结构和相似的生理，两个不相关的间隙连接蛋白家族存在于动物王国。脊椎动物间隙连接由连接蛋白家族的成员形成，而无脊椎动物间隙连接由连接蛋白蛋白组成。在这里，我们报告的克隆两个连接蛋白水蛭medicidae。这些连接蛋白在水蛭中枢神经系统中显示出差异表达：Hm-inx 1在中枢神经系统中的每个神经元中表达，但在神经胶质中不表达，而Hm-inx 2在神经胶质中表达，但在神经元中不表达。在成对的爪蟾卵母细胞系统中的异源表达表明，两种连接蛋白都能够形成功能性同型间隙连接。Hm-inx 1形成不强门控的通道。相反，Hm-inx 2形成的通道是高度电压依赖性的，这些通道表现出类似于双整流器的特性。此外，Hm-inx 1和Hm-inx 2能够合作形成爪蟾卵母细胞中的异型缝隙连接。这些通道的行为主要是预测从组成hemichannels的属性，但也证明了两者之间的相互作用的证据。这项工作代表了第一次演示的功能间隙连接蛋白从Lophotrochozoan动物和支持的假设，连接蛋白为基础的通信仅限于后口分支。
Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leech Hirudo medicinalis. These innexins show a differential expression in the leech CNS: Hm-inx1 is expressed by every neuron in the CNS but not in glia, whereas Hm-inx2 is expressed in glia but not neurons. Heterologous expression in the paired Xenopus oocyte system demonstrated that both innexins are able to form functional homotypic gap junctions. Hm-inx1 forms channels that are not strongly gated. In contrast, Hm-inx2 forms channels that are highly voltage-dependent; these channels demonstrate properties resembling those of a double rectifier. In addition, Hm-inx1 and Hm-inx2 are able to cooperate to form heterotypic gap junctions in Xenopus oocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two.This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade.