Candi E, Tarcsa E, Digiovanna J J, Compton J G, Elias P M, Marekov L N, Steinert P M
Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2752, USA.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2067-72. doi: 10.1073/pnas.95.5.2067.
We have addressed the question of how keratin intermediate filaments are associated with the cell envelope at the periphery of cornified epidermal cells. Many peptides from human epidermal cell envelopes containing isopeptide crosslinks inserted by transglutaminases in vivo have been characterized. A major subset involves the type II keratin chains keratin 1, 2e, 5, or 6 crosslinked to several protein partners through a lysine residue located in a conserved region of the V1 subdomain of their head domains. This sequence specificity was confirmed in in vitro crosslinking experiments. Previously the causative mutation in a family with diffuse nonepidermolytic palmar-plantar keratoderma was shown to be the loss in one allele of the same lysine residue of the keratin 1 chain. Ultrastructural studies of affected palm epidermis have revealed abnormalities in the organization of keratin filaments subjacent to the cell envelope and in the shape of the cornified cells. Together, these data suggest a mechanism for the coordination of cornified cell structure by permanent covalent attachment of the keratin intermediate filament cytoskeleton to the cell envelope by transglutaminase crosslinking. Furthermore, these studies identify the essential role of a conserved lysine residue on the head domains of type II keratins in the supramolecular organization of keratin filaments in cells.
我们已经探讨了角质形成中间丝如何与角质化表皮细胞周边的细胞包膜相关联的问题。许多来自人类表皮细胞包膜的含有体内转谷氨酰胺酶插入的异肽交联的肽段已被鉴定。一个主要的亚组涉及II型角蛋白链角蛋白1、2e、5或6，它们通过位于其头部结构域V1亚结构域保守区域的赖氨酸残基与几个蛋白质伴侣交联。这种序列特异性在体外交联实验中得到了证实。先前在一个患有弥漫性非表皮松解性掌跖角化病的家族中，致病突变被证明是角蛋白1链相同赖氨酸残基的一个等位基因缺失。对受影响手掌表皮的超微结构研究揭示了细胞包膜下方角蛋白丝组织以及角质化细胞形状的异常。综上所述，这些数据表明了一种机制，即通过转谷氨酰胺酶交联将角蛋白中间丝细胞骨架永久共价连接到细胞包膜，从而协调角质化细胞结构。此外，这些研究确定了II型角蛋白头部结构域上保守赖氨酸残基在细胞角蛋白丝超分子组织中的重要作用。
