Bierkamp C, Schwarz H, Huber O, Kemler R
Max Planck Institute of Immunobiology, Department of Molecular Embryology, Stübeweg 51, D-79108 Freiburg and Max Planck Institute of Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
Development. 1999 Jan;126(2):371-81. doi: 10.1242/dev.126.2.371.
Plakoglobin, a protein belonging to the Armadillo-repeat gene family, is the only component that adherens junctions and desmosomes have in common. Plakoglobin null-mutant mouse embryos die because of severe heart defects and may exhibit an additional skin phenotype, depending on the genetic background. Lack of plakoglobin affects the number and structure of desmosomes, resulting in visible defects when cells are subjected to increasing mechanical stress, e.g. when embryonic blood starts circulating or during skin differentiation. By analysing plakoglobin-negative embryonic skin differentiation in more detail, we show here that, in the absence of plakoglobin, its closest homologue, beta-catenin, becomes localized to desmosomes and associated with desmoglein. This substitution may account for the relatively late appearance of the developmental defects seen in plakoglobin null-mutant embryos. beta-catenin cannot, however, fully compensate a lack of plakoglobin. In the absence of plakoglobin, there was reduced cell-cell adhesion, resulting in large intercellular spaces between keratinocytes, subcorneal acantholysis and necrosis in the granular layer of the skin. Electron microscopic analysis documented a reduced number of desmosomes, and those present lacked the inner dense plaque and had fewer keratin filaments anchored. Our analysis underlines the central role of plakoglobin for desmosomal assembly and function during embryogenesis.
桥粒斑珠蛋白是一种属于犰狳重复基因家族的蛋白质，是黏着连接和桥粒唯一共有的成分。桥粒斑珠蛋白基因敲除的小鼠胚胎因严重心脏缺陷而死亡，并且根据遗传背景的不同，可能还会表现出额外的皮肤表型。缺乏桥粒斑珠蛋白会影响桥粒的数量和结构，当细胞受到不断增加的机械应力时，例如胚胎血液开始循环时或皮肤分化过程中，就会导致明显的缺陷。通过更详细地分析桥粒斑珠蛋白阴性的胚胎皮肤分化情况，我们在此表明，在缺乏桥粒斑珠蛋白的情况下，其最接近的同源物β-连环蛋白会定位于桥粒并与桥粒芯糖蛋白相关联。这种替代可能解释了在桥粒斑珠蛋白基因敲除的胚胎中出现发育缺陷相对较晚的原因。然而，β-连环蛋白不能完全弥补桥粒斑珠蛋白的缺失。在缺乏桥粒斑珠蛋白的情况下，细胞间黏附减少，导致角质形成细胞之间出现大的细胞间隙、角层下棘层松解以及皮肤颗粒层坏死。电子显微镜分析记录了桥粒数量减少，并且存在的桥粒缺乏内部致密斑，锚定的角蛋白丝也较少。我们的分析强调了桥粒斑珠蛋白在胚胎发育过程中对桥粒组装和功能的核心作用。
