Ishida-Yamamoto A, Takahashi H, Iizuka H
Department of Dermatology, Asahikawa Medical College, Japan.
Histol Histopathol. 1998 Jul;13(3):819-26. doi: 10.14670/HH-13.819.
The cornified cell envelope (CE) is a tough structure formed beneath the plasma membrane of terminally differentiated keratinocytes. Recent progress in understanding the molecular organization of the CE has disclosed the complex, yet orderly structure that functions as a protective barrier against the environment. We have recently demonstrated that two inherited skin diseases, Vohwinkel's syndrome (VS) and progressive symmetric erythrokeratoderma (PSEK) may result from mutations in the gene encoding loricrin, a major constituent of the CE. In adult human epidermis, loricrin is diffusely distributed within the superficial granular cells. In the cornified cells, loricrin is associated with CEs. In some patients with VS and PSEK skin, however, granular cells contain many intranuclear granules which are labeled with an amino-terminal loricrin antibody. CEs are thinner than normal and sparsely labeled with the loricrin antibody. Parakeratotic cornified cells contain loricrin-positive granules. Sequencing of the loricrin gene has disclosed heterozygous mutations; insertion of one nucleotide (730insG, 709insC) that shifts the reading frame in these patients. Consequently the carboxyl-terminus are replaced by highly charged missense sequences that override the endogeneous termination codon extending the protein with an additional 22 amino acids. Elucidation of the molecular biology of "loricrin keratodermas" adds to our understanding of the complexity and biological significance of the CE.
角质化细胞包膜（CE）是在终末分化角质形成细胞的质膜下方形成的一种坚韧结构。在理解CE分子组织方面的最新进展揭示了其复杂但有序的结构，该结构起着抵御外界环境的保护屏障作用。我们最近证明，两种遗传性皮肤病，沃温克尔综合征（VS）和进行性对称性红斑角化病（PSEK）可能是由于编码兜甲蛋白（CE的主要成分）的基因突变所致。在成人人类表皮中，兜甲蛋白在浅表颗粒细胞内呈弥漫性分布。在角质化细胞中，兜甲蛋白与CE相关。然而，在一些VS和PSEK患者的皮肤中，颗粒细胞含有许多被氨基末端兜甲蛋白抗体标记的核内颗粒。CE比正常情况更薄，用兜甲蛋白抗体标记稀疏。角化不全的角质化细胞含有兜甲蛋白阳性颗粒。兜甲蛋白基因测序揭示了杂合突变；一个核苷酸的插入（730insG，709insC），这在这些患者中改变了阅读框。因此，羧基末端被高度带电的错义序列取代，并取代了内源性终止密码子，使蛋白质额外延长了22个氨基酸。对“兜甲蛋白角化病”分子生物学的阐明增加了我们对CE复杂性和生物学意义的理解。
