The function of plakophilin 1 in desmosome assembly and actin filament organization
The function of plakophilin 1 in desmosome assembly and actin filament organization
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DOI：
10.1083/jcb.149.1.209
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发表时间：
2000-04-03
影响因子：
7.8
通讯作者：
Vinzens, U
中科院分区：
文献类型：
--
作者：
Hatzfeld, M;Haffner, C;Vinzens, U
Plakophilin 1是犰狳多基因家族的成员，是一种在细胞核和桥粒中具有双重定位的蛋白质。为了阐明其在桥粒组装和调控中的作用，我们分析了其在体内的定位和结合伙伴。当在HaCaT角质形成细胞中过表达时，plakophilin 1定位于细胞核和桥粒，并显著增强了桥粒蛋白向质膜的募集。在酵母双杂交系统中，这种作用是由斑嗜蛋白1的头部结构域介导的，该头部结构域与桥粒芯糖蛋白1、桥粒斑蛋白和角蛋白相互作用。过表达的犰狳重复结构域诱导显着的显性负表型与丝状伪足和长细胞突起的形成，其中plakophilin 1与肌动蛋白丝共定位。这种表型是严格依赖于一个保守的基序在中心的犰狳重复结构域。我们的研究结果表明，plakophilin 1包含两个功能不同的域：头域，这可能发挥作用，在组织桥粒斑块的基底上细胞，和犰狳重复结构域，这可能是参与调节肌动蛋白细胞骨架的动态。
Plakophilin 1, a member of the ar armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced the recruitment of desmosomal proteins to the plasma membrane. This effect was mediated by plakophilin 1's head domain, which interacted with desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Overexpression of the armadillo repeat domain induced a striking dominant negative pheno-type with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.