Interaction between connexin35 and zonula occludens-1 and its potential role in the regulation of electrical synapses
Interaction between connexin35 and zonula occludens-1 and its potential role in the regulation of electrical synapses
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DOI：
10.1073/pnas.0804793105
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发表时间：
2008-08-26
影响因子：
11.1
通讯作者：
Pereda, Alberto E.
中科院分区：
文献类型：
--
作者：
Flores, Carmen E.;Li, Xinbo;Pereda, Alberto E.
尽管已知化学传递的调节涉及受体与支架蛋白的相互作用，但对调节间隙连接介导的电突触中蛋白质-蛋白质相互作用的存在知之甚少。据报道，MAGUK蛋白家族的一个成员，支架蛋白zonula-occludens-1（ZO-1）与几种连接蛋白（Cxs）相互作用。我们在这里表明，ZO-1广泛共定位Cx 35在可识别的“混合”（电气和化学）接触金鱼Mauthner细胞，模型突触的脊椎动物电传输的研究，它是可能的相关生理特性与分子组成。此外，我们的分析表明，这些蛋白质直接在金鱼电突触相互作用。与Cx43通过PDZ 2结构域与ZO-1相互作用相反，Cx 35通过PDZ 1结构域与ZO-1相互作用，并且这种结合具有较低的亲和力。ZO-1/Cx 35协会的属性表明这两种蛋白质之间存在更动态的关系，可能包括ZO-1在调节这些高度可变的电突触间隙连接电导的作用。ZO-1与Cx 35/Cx 36同源物C端保守区域的相互作用可能在哺乳动物和其他脊椎动物的电突触中具有共同的功能。
Although regulation of chemical transmission is known to involve the interaction of receptors with scaffold proteins, little is known about the existence of protein-protein interactions in regulating gap junction-mediated electrical synapses. The scaffold protein zonula-occludens-1 (ZO-1), a member of the MAGUK family of proteins, was reported to interact with several connexins (Cxs). We show here that ZO-1 extensively colocalizes with Cx35 at identifiable "mixed" (electrical and chemical) contacts on goldfish Mauthner cells, a model synapse for the study of vertebrate electrical transmission where it is possible to correlate physiological properties with molecular composition. Further, our analysis indicates that these proteins directly interact at goldfish electrical synapses. In contrast to Cx43, which interacts with ZO-1 via the PDZ2 domain, Cx35 interacts with ZO-1 via the PDZ1 domain, and this association is of lower affinity. The properties of the ZO-1/Cx35 association suggest the existence of a more dynamic relation between these two proteins, possibly including a role of ZO-1 in regulating gap junctional conductance at these highly modifiable electrical synapses. The interaction of ZO-1 with conserved regions of the C termini of Cx35/Cx36 orthologs may have a common function at electrical synapses of mammals and other vertebrates.