A unique and specific interaction between αT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs
A unique and specific interaction between αT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs
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DOI：
10.1242/jcs.004713
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发表时间：
2007-06-15
影响因子：
4
通讯作者：
van Roy, Frans
中科院分区：
文献类型：
--
作者：
Goossens, Steven;Janssens, Barbara;van Roy, Frans
-连环蛋白在钙粘蛋白-连环蛋白-细胞粘附复合物中起关键作用。我们之前报道了α T-catenin， α -catenin蛋白家族的新成员。T-catenin主要在心肌细胞中表达，与E-catenin在间插盘处共定位。α T-和α e -连环蛋白是否具有特异性或协同功能尚不清楚。在这项研究中，我们使用酵母双杂交方法来鉴定α T-catenin的特定功能。观察到α t -连环蛋白和嗜血小板蛋白之间的相互作用，并随后通过共免疫沉淀和共定位证实。与嗜血小板蛋白氨基末端的相互作用似乎对α t -连环蛋白的中心“粘附调节”域具有特异性。此外，我们通过免疫电镜显示，心脏中的桥粒蛋白不仅定位于嵌入盘中的桥粒，而且也定位于具有杂交成分的粘附连接处。我们发现在后一种连接中，内源性plakophilin-2与α T-catenin共定位。通过在cadherin-catenin复合物和中间丝之间提供额外的连接，α T-catenin与plakophilin-2的结合被认为是调节和加强心肌细胞之间细胞间粘附的一种手段。这可以解释plakophilin-2突变对嵌入椎间盘细胞连接稳定性的破坏性影响，从而导致心肌功能障碍。
Alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion complexes. We previously reported on alpha T-catenin, a novel member of the alpha-catenin protein family. alpha T-catenin is expressed predominantly in cardiomyocytes, where it colocalizes with alpha E-catenin at the intercalated discs. Whether alpha T- and alpha E-catenin have specific or synergistic functions remains unknown. In this study we used the yeast two-hybrid approach to identify specific functions of alpha T-catenin. An interaction between alpha T-catenin and plakophilins was observed and subsequently confirmed by co-immunoprecipitation and colocalization. Interaction with the amino-terminal part of plakophilins appeared to be specific for the central `adhesion-modulation' domain of alpha T-catenin. In addition, we showed, by immuno-electron microscopy, that desmosomal proteins in the heart localize not only to the desmosomes in the intercalated discs but also at adhering junctions with hybrid composition. We found that in the latter junctions, endogenous plakophilin-2 colocalizes with alpha T-catenin. By providing an extra link between the cadherin-catenin complex and intermediate filaments, the binding of alpha T-catenin to plakophilin-2 is proposed to be a means of modulating and strengthening cell-cell adhesion between cardiac muscle cells. This could explain the devastating effect of plakophilin-2 mutations on cell junction stability in intercalated discs, which lead to cardiac muscle malfunction.