Assessment of splice variant-specific functions of desmocollin 1 in the skin
Assessment of splice variant-specific functions of desmocollin 1 in the skin
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DOI：
10.1128/mcb.24.1.154-163.2004
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发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Koch, PJ
中科院分区：
文献类型：
--
作者：
Cheng, X;Mihindukulasuriya, K;Koch, PJ
Desmocollin 1 (Dsc1) 是在复层上皮终末分化角质形成细胞中形成的桥粒细胞粘附受体的一部分。 dsc1 基因编码两种蛋白质（Dsc1a 和 Dsc1b），它们的不同之处仅在于它们的 COOH 末端细胞质氨基酸序列。根据体外实验，人们认为 Dsc1a 变体对于桥粒斑块的组装至关重要，桥粒斑块是将桥粒连接到上皮细胞的中间丝细胞骨架的结构。我们已经培育出合成截短的 Dsc1 受体的小鼠，该受体缺乏 Dsc1a 和 Dsc1b 特异性 COOH 末端结构域。这种突变的跨膜受体不结合常见的桥粒斑蛋白 plakoglobin 和 plakophilin 1，但被整合到功能性桥粒中。有趣的是，我们的突变小鼠没有表现出先前在 dsc1 缺失小鼠中观察到的表皮脆弱性。这表明 Dsc1a 和 Dsc1b 特异性 COOH 末端胞质结构域都不是建立和维持桥粒粘附所必需的。然而，我们的突变体与 dsc1-null 小鼠的比较表明，Dsc1 胞外结构域对于维持皮肤结构完整性是必需的。
Desmocollin 1 (Dsc1) is part of a desmosomal cell adhesion receptor formed in terminally differentiating keratinocytes of stratified epithelia. The dsc1 gene encodes two proteins (Dsc1a and Dsc1b) that differ only with respect to their COOH-terminal cytoplasmic amino acid sequences. On the basis of in vitro experiments, it is thought that the Dsc1a variant is essential for assembly of the desmosomal plaque, a structure that connects desmosomes to the intermediate filament cytoskeleton of epithelial cells. We have generated mice that synthesize a truncated Dsc1 receptor that lacks both the Dsc1a- and Dsc1b-specific COOH-terminal domains. This mutant transmembrane receptor, which does not bind the common desmosomal plaque proteins plakoglobin and plakophilin 1, is integrated into functional desmosomes. Interestingly, our mutant mice did not show the epidermal fragility previously observed in dsc1-null mice. This suggests that neither the Dsc1a- nor the Dsc1b-specific COOH-terminal cytoplasmic domain is required for establishing and maintaining desmosomal adhesion. However, a comparison of our mutants with dsc1-null mice suggests that the Dsc1 extracellular domain is necessary to maintain structural integrity of the skin.