Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells
Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells
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DOI：
10.1161/circresaha.107.154252
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发表时间：
2007-09-28
影响因子：
20.1
通讯作者：
Delmar, Mario
中科院分区：
文献类型：
--
作者：
Oxford, Eva M.;Musa, Hassan;Delmar, Mario
桥粒和缝隙连接是心脏闰盘的不同结构成分。在这里，我们问是否存在的plakophilin（PKP）2，桥粒的一个组成部分，是必不可少的适当功能和分布的差距连接蛋白（Cx）43。我们使用RNA沉默技术来降低从新生大鼠心脏获得的心脏细胞（心室肌细胞以及心外膜衍生细胞）中PKP2的表达。我们评估了Cx43缝隙连接的含量、分布和功能。我们的研究结果表明，PKP2表达的损失导致总Cx43含量的减少，Cx43的细胞内空间的显着重新分配，并减少细胞之间的染料偶联。单独的实验表明，Cx43和PKP2可以共存于同一大分子复合物中。我们的研究结果支持桥粒和间隙连接蛋白之间的分子串扰的概念。结果进行了讨论的背景下，致炎性右心室心肌病，遗传性疾病涉及突变的桥粒蛋白，包括PKP2。
Desmosomes and gap junctions are distinct structural components of the cardiac intercalated disc. Here, we asked whether the presence of plakophilin (PKP) 2, a component of the desmosome, is essential for the proper function and distribution of the gap junction protein connexin (Cx) 43. We used RNA silencing technology to decrease the expression of PKP2 in cardiac cells (ventricular myocytes, as well as epicardium-derived cells) obtained from neonatal rat hearts. We evaluated the content, distribution, and function of Cx43 gap junctions. Our results show that loss of PKP2 expression led to a decrease in total Cx43 content, a significant redistribution of Cx43 to the intracellular space, and a decrease in dye coupling between cells. Separate experiments showed that Cx43 and PKP2 can coexist in the same macromolecular complex. Our results support the notion of a molecular crosstalk between desmosomal and gap junction proteins. The results are discussed in the context of arrhythmogenic right ventricular cardiomyopathy, an inherited disease involving mutations in desmosomal proteins, including PKP2.