Helmholtz Group for Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Eur J Cell Biol. 2010 May;89(5):365-78. doi: 10.1016/j.ejcb.2009.11.025. Epub 2010 Feb 2.
Postnatal development of mammalian cardiomyocytes in the working myocardium is characterized by a near-complete translocation of both kinds of adhering junctions (AJs), i.e. desmosomes and fasciae adhaerentes (FAs), to the polar intercalated disk (ID) regions where they cluster, fuse and molecularly amalgamate to extended hybrid intercellular junction structures, the area composita (composite junction; AC). Using immunofluorescence and immunoelectron microscopy we now report that the AJ structures of the conduction system, in particular those of the Purkinje fiber cells of cows and sheep are fundamentally different. Here the numerous AJs remain in lateral connections with other conductive cells. Desmosomal or desmosome-like junctions can still be distinguished from FA junctions, and a third type of AJs can be identified which shows colocalization of desmosomal and FA proteins, i.e. an AC character. These results, together with demonstrations of other cell type cytoskeletal markers such as alpha-cardiac actin and desmin, support the concept that conductive cells are derived from embryonal cardiomyocytes and are arrested at an early stage of differentiation. We also show that the conductive cells have extended plasma membrane regions characterized by an exceptionally high proportion of junctions with desmosomal character and proteins, amounting to 50% and more, resulting in the highest desmosome protein packing so far described in non-epithelial cells. The relevance of these junctions for the formation, maintenance and functions of the conductive system is discussed, together with the conclusion that the desmosome-rich regions of conductive cells are among the most vulnerable sites for functional disorders caused by desmosomal protein mutations.
哺乳动物工作心肌细胞的出生后发育的特征是两种粘着连接(AJs),即桥粒和粘着斑(FAs)几乎完全转位到极性闰盘(ID)区域,在那里它们聚集、融合并在分子上合并成扩展的混合细胞间连接结构,即复合连接(AC)。使用免疫荧光和免疫电子显微镜,我们现在报告说,传导系统的 AJ 结构,特别是牛和羊的浦肯野纤维细胞的 AJ 结构在根本上是不同的。在这里,许多 AJ 仍然与其他传导细胞保持侧向连接。可以从 FA 连接区分出桥粒或桥粒样连接,并且可以识别出第三种 AJ,其显示桥粒和 FA 蛋白的共定位,即 AC 特征。这些结果,以及其他细胞类型细胞骨架标志物如α-心脏肌动蛋白和结蛋白的证明,支持了传导细胞来源于胚胎心肌细胞并在分化的早期阶段停滞的概念。我们还表明,传导细胞具有扩展的质膜区域,其特征是具有桥粒特征和蛋白的连接特别高的比例,达到 50%或更多,导致迄今为止在非上皮细胞中描述的最高桥粒蛋白包装。讨论了这些连接对于传导系统的形成、维持和功能的相关性,并得出结论,即传导细胞的富含桥粒的区域是由于桥粒蛋白突变引起的功能障碍的最脆弱部位之一。