Differentially expressed late constituents of the epidermal cornified envelope
Differentially expressed late constituents of the epidermal cornified envelope
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DOI：
10.1073/pnas.231489198
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发表时间：
2001-11-06
影响因子：
11.1
通讯作者：
Byrne, C
中科院分区：
文献类型：
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作者：
Marshall, D;Hardman, MJ;Byrne, C
皮肤的屏障活性和形成内部屏障的上皮衬里是由脂质-角质细胞结构(皮肤中的角质层)赋予的。角膜细胞的完整性依赖于外角化的包膜，对于维持屏障功能是必不可少的。在表皮发育和分化过程中，蛋白质通过表皮谷氨酰胺转氨酶的作用顺序地结合到包膜中，这一过程得到了很好的证明。然而，最近主要角化的包膜成分的敲除未能显著干扰屏障功能，这表明还有其他未知成分参与其中。我们报道了在人类1q21的表皮分化复合体中的一个新的基因簇，编码了一个由18个蛋白质组成的家族，这些蛋白质是表皮转谷氨酰胺酶的底物。在表皮分化过程中，这些蛋白质进入角化的包膜，在发育后期和包膜成熟过程的后期。根据表达模式，这些基因聚集在表皮分化复合体中，即表皮表达的蛋白质聚集在一起，而来自内部屏障形成上皮的蛋白质也聚集在一起。我们认为，这些蛋白质调节动物表面的屏障活性，其方式类似于为特征良好的角化包膜前体所建议的方式，即富含脯氨酸的小蛋白。为了强调这些蛋白质在包膜组装后期的并入，我们将这些人类蛋白质称为晚期包膜蛋白。
Barrier activity of skin and internal barrier-forming epithelial linings are conferred by a lipid-corneocyte structure (stratum corneum In skin). The integrity of the corneocytes depends on the outer cornified envelope and is essential for maintenance of barrier function. During epidermal development and differentiation, proteins are sequentially incorporated into the envelope via action of epidermal transglutaminases in a well documented process. However, recent knockouts of major cornified envelope constituents have failed to disrupt barrier function significantly, suggesting that additional unidentified components are involved. We report a new gene cluster in the epidermal differentiation complex at human 1q21 encoding a family of 18 proteins that are substrates for epidermal transglutaminases. These proteins incorporate into the cornified envelope late in development and late in the process of envelope maturation during epidermal differentiation. The genes cluster within the epidermal differentiation complex according to expression pattern, i.e., epidermally expressed proteins cluster together while proteins from internal barrier-forming epithelia also cluster. We propose that these proteins modulate barrier activity over the surface of the animal, in a manner analogous to that proposed for the well characterized cornified envelope precursors, the small proline-rich proteins. To emphasize the incorporation of these proteins late in envelope assembly, we call the human proteins late envelope proteins.