Sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and keratin 1 deimination
Sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and keratin 1 deimination
复制标题
DOI：
10.1046/j.0022-202x.2001.01671.x
复制
发表时间：
2002-02-01
影响因子：
6.5
通讯作者：
Iizuka, H
中科院分区：
文献类型：
--
作者：
Ishida-Yamamoto, A;Senshu, T;Iizuka, H
角质形成细胞分化的最后一步，即从颗粒细胞向皮质细胞的转变，涉及各种翻译后修饰，包括精氨酸残基的脱亚胺化。主要的脱亚氨基表皮蛋白衍生自K1。在小鼠K1中鉴定了两个优选的脱亚胺位点，一个在V1亚结构域中，另一个在V2亚结构域中。针对V2亚结构域中的脱亚氨基肽序列的抗体不仅识别脱亚氨基小鼠K1，而且识别脱亚氨基人K1。在这项研究中，我们分析了分布的脱亚胺K1在正常人皮肤和大疱性先天性鱼鳞病样红皮病在光镜和电镜水平。在正常皮肤中，前几个（1-3）角质细胞层对聚丝蛋白呈阳性，对脱亚氨基小鼠K1肽抗体呈阴性，而更表层的细胞对聚丝蛋白呈阴性，对脱亚氨基小鼠K1肽抗体呈强阳性，表明在角质化的初始阶段K1脱亚氨基作用的发生略有延迟。在大疱性先天性鱼鳞病样硬皮病中，聚丝蛋白不能正确压实的聚集角蛋白对脱亚氨基小鼠K1肽抗体呈弱阳性。此外，在免疫印迹分析中，与正常对照相比，大疱性先天性鱼鳞病样红皮病中的K1衍生物与抗脱亚胺小鼠K1肽的抗体反应较差。我们的研究结果表明，顺序重组的cornea细胞角蛋白丝，涉及丝蛋白介导的压实和K1脱亚胺。大疱性先天性鱼鳞病样红皮病的异常角蛋白聚集可能会干扰K1的正常脱亚胺化。
The final step of keratinocyte differentiation, transition from the granular cells to the cornified cells, involves various post-translational modifications that include deimination of arginine residues. Major deiminated epidermal proteins are derived from K1. Two preferred deimination sites were identified in mouse K1, one in the V1 and the other in the V2 subdomains. An antibody against the deiminated peptide sequence in the V2 subdomain recognized not only deiminated mouse K1 but also deiminated human K1. In this study we analyzed distribution of deiminated K1 in normal human skin and in bullous congenital ichthyosiform erythroderma at light and electron microscopic levels. In normal skin the first few (1-3) cornified cell layers were positive for filaggrin and negative for the antibody against deiminated mouse K1 peptide, whereas the more superficial cells were negative for filaggrin and strongly positive for the antibody against deiminated mouse K1 peptide, indicating slightly delayed onset of K1 deimination at the initial stage of cornification. The clumped keratin in bullous congenital ichthyosiform crythroderma that was not properly compacted with filaggrin was poorly positive to the antibody against deiminated mouse K1 peptide. In addition, K1 derivatives in bullous congenital ichthyosiform erythroderma reacted poorly with the antibody against deiminated mouse K1 peptide compared with the normal control in immunoblot analyses. Our results suggest sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and K1 deimination. Abnormal keratin aggregation in bullous congenital ichthyosiform erythroderma is likely to disturb the normal deimination of K1.