The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes - Implications for cutaneous disease
The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes - Implications for cutaneous disease
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DOI：
10.1074/jbc.274.26.18145
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发表时间：
1999-06-25
影响因子：
4.8
通讯作者：
Green, KJ
中科院分区：
文献类型：
--
作者：
Kowalczyk, AP;Hatzfeld, M;Green, KJ
桥粒对表皮完整性的贡献在与 plakophilin-1 功能基因缺失相关的遗传性水疱性疾病中很明显。为了确定 plakophilin-1 在桥粒组装中的功能，检查了桥粒钙粘蛋白、桥斑蛋白以及犰狳家族成员 plakoglobin 和 plakophilin-1 之间的相互作用。在瞬时表达测定中，plakophilin-1 与桥粒斑蛋白氨基末端结构域形成复合物，并增强其向细胞-细胞边界的募集；这种募集不依赖于桥粒钙粘蛋白的等摩尔表达。与桥粒斑蛋白-斑球蛋白相互作用相反，桥粒斑蛋白和 plakophilin-1 之间的相互作用不是由 plakophilin-1 的犰狳重复结构域介导的，而是由非犰狳头部结构域介导，如通过酵母双杂交和招募测定评估的。我们提出了一个模型，其中 plakoglobin 作为钙粘蛋白和桥粒斑蛋白之间的连接物，而 plakophilin-1 则增强桥粒斑蛋白分子之间的横向相互作用。该模型表明，缺乏 plakophilin-1 的患者的表皮病变是由于桥粒处桥粒斑蛋白和中间丝的结合位点减少而导致完整性丧失的结果。
The contribution of desmosomes to epidermal integrity is evident in the inherited blistering disorder associated with the absence of a functional gene for plakophilin-1. To define the function of plakophilin-1 in desmosome assembly, interactions among the desmosomal cadherins, desmoplakin, and the armadillo family members plakoglobin and plakophilin-1 were examined. In transient expression assays, plakophilin-1 formed complexes with a desmoplakin amino-terminal domain and enhanced its recruitment to cell-cell borders; this recruitment was not dependent on the equimolar expression of desmosomal cadherins. In contrast to desmoplakin-plakoglobin interactions, the interaction between desmoplakin and plakophilin-1 was not mediated by the armadillo repeat domain of plakophilin-1 but by the non-armadillo head domain, as assessed by yeast two-hybrid and recruitment assays. We propose a model whereby plakoglobin serves as a linker between the cadherins and desmoplakin, whereas plakophilin-1 enhances lateral interactions between desmoplakin molecules. This model suggests that epidermal lesions in patients lacking plakophilin-1 are a consequence of the loss of integrity resulting from a decrease in binding sites for desmoplakin and intermediate filaments at desmosomes.