Puttagunta S, Mathur M, Cowin P
Department of Cell Biology, Ronald O. Perelman Department of Dermatology, New York University Medical Center, New York 10016.
J Biol Chem. 1994 Jan 21;269(3):1949-55.
The cadherin superfamily of calcium-dependent cell-cell adhesion and recognition proteins can be categorized into a number of subsets on the basis of the distinct cytoplasmic sequences of their members. Currently these families include classical cadherins, desmogleins, desmocollins, protocadherins, and the products of the Drosophila genes FAT and Dachsous. Dsg1, the prototype of the desmoglein family, is a major component of epidermal desmosomes and the antigenic target of antibodies found in the sera of patients with the blistering disease, pemphigus foliaceus. In this study, we determined the organization of the bovine DSG1 gene. This gene consists of 15 exons distributed over > 37.5 kilobases of genomic DNA. A comparison of DSG1 with genes encoding classical cadherins revealed a striking conservation of exon boundaries in regions encoding the ectodomain and to a more limited extent among those encoding the cytoplasmic domain. Polymorphism was found in a sequence of DSG1 encoding protein proximal to the external face of the plasma membrane. This region is topologically equivalent to a domain of classical cadherins that harbors epitopes recognized by adhesion-disrupting antibodies. We discuss these results with regard to the evolution of the cadherin superfamily and their implications for the definition of pemphigus epitopes.
钙依赖性细胞间黏附与识别蛋白的钙黏蛋白超家族可根据其成员不同的胞质序列分为若干亚组。目前这些家族包括经典钙黏蛋白、桥粒芯糖蛋白、桥粒胶蛋白、原钙黏蛋白以及果蝇基因FAT和Dachsous的产物。桥粒芯糖蛋白家族的原型Dsg1是表皮桥粒的主要成分，也是落叶型天疱疮患者血清中发现的抗体的抗原靶点。在本研究中，我们确定了牛DSG1基因的结构。该基因由15个外显子组成，分布在超过37.5千碱基的基因组DNA上。将DSG1与编码经典钙黏蛋白的基因进行比较发现，在编码胞外结构域的区域外显子边界具有显著的保守性，而在编码胞质结构域的区域保守性则较为有限。在编码靠近质膜外表面蛋白质的DSG1序列中发现了多态性。该区域在拓扑结构上等同于经典钙黏蛋白的一个结构域，该结构域含有被破坏黏附的抗体识别的表位。我们讨论了这些结果与钙黏蛋白超家族进化的关系及其对天疱疮表位定义的影响。
