McGrath J A, McMillan J R, Shemanko C S, Runswick S K, Leigh I M, Lane E B, Garrod D R, Eady R A
Department of Cell Pathology, St. John's Institute of Dermatology (United Medical and Dental School), St. Thomas's Hospital, London, UK.
Nat Genet. 1997 Oct;17(2):240-4. doi: 10.1038/ng1097-240.
Members of the armadillo protein gene family, which includes plakoglobin and beta-catenin, have important functions in cytoskeleton/cell membrane interactions. These proteins may act as linker molecules at adherens junctions and desmosomes at the plasma membrane; in addition, they may have pivotal roles in signal transduction pathways and significant effects on cell behaviour during development. Here, we describe the first human mutations in one of these dual function proteins, plakophilin 1 (band-6 protein; refs 8-10). The affected individual has a complete absence of immunostaining for plakophilin 1 in the skin and is a compound heterozygote for autosomal-recessively inherited premature termination codons of translation on both alleles of the plakophilin 1 gene (PKP1). Clinically, there are features of both cutaneous fragility and congenital ectodermal dysplasia affecting skin, hair and nails. There is no evidence of significant abnormalities in other epithelia or tissues. Desmosomes in the skin are small and poorly formed with widening of keratinocyte intercellular spaces and perturbed desmosome/keratin intermediate filament interactions. The molecular findings and clinical observations in this patient attest to the dual importance of plakophilin 1 in both cutaneous cell-call adhesion and epidermal morphogenesis.
犰狳蛋白基因家族的成员，包括桥粒斑珠蛋白和β-连环蛋白，在细胞骨架/细胞膜相互作用中具有重要功能。这些蛋白质可能作为质膜上黏附连接和桥粒处的连接分子；此外，它们可能在信号转导途径中起关键作用，并在发育过程中对细胞行为产生重大影响。在此，我们描述了这些双功能蛋白之一桥粒芯蛋白1（6带蛋白；参考文献8 - 10）的首例人类突变。受影响个体的皮肤中完全没有桥粒芯蛋白1的免疫染色，并且是桥粒芯蛋白1基因（PKP1）两个等位基因上常染色体隐性遗传的翻译提前终止密码子的复合杂合子。临床上，有皮肤脆弱以及影响皮肤毛发和指甲的先天性外胚层发育不良的特征。没有证据表明其他上皮或组织存在明显异常。皮肤中的桥粒较小且形成不良，角质形成细胞间间隙增宽，桥粒/角蛋白中间丝相互作用紊乱。该患者的分子研究结果和临床观察证明了桥粒芯蛋白1在皮肤细胞间黏附和表皮形态发生中的双重重要性。
