The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations
The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations
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DOI：
10.1007/s00018-005-5196-y
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发表时间：
2005-09-01
影响因子：
8
通讯作者：
Simon, M
中科院分区：
文献类型：
--
作者：
Méchin, MC;Enji, M;Simon, M
脱亚胺化是一种由肽基精氨酸脱亚胺酶 (PAD) 催化的翻译后修饰，是表皮分化最后步骤中关键的 Ca2+ 依赖性事件。在正常人表皮中，脱亚胺化蛋白是丝聚蛋白和角蛋白，PAD 1、2 和 3 被表达，但它们的相对作用尚不清楚。这三种 PAD 以活性重组形式生产，表现出独特的合成底物特异性、丝聚合蛋白脱亚氨基的不同效率以及特定的钙和 pH 敏感性。免疫电子显微镜表明，PAD1 和 PAD3 与丝聚蛋白共定位于较深层角质细胞的丝状基质内，蛋白质在此被脱亚胺化。这一结果强烈表明，两种同工型均参与丝聚蛋白的脱亚胺化，这是导致表皮屏障功能所需的游离氨基酸产生的重要步骤。此外，PAD1 被证明持续存在于上层角质细胞，在那里它使角蛋白 K1 去亚胺化，这种修饰被认为与基质的超微结构变化有关。
Deimination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), appears as a crucial Ca2+-dependent event in the last steps of epidermal differentiation. In normal human epidermis, where the deiminated proteins are filaggrin and keratins, PAD 1, 2 and 3 are expressed but their relative role is unknown. The three PADs, produced as active recombinant forms, showed distinct synthetic-substrate specificities, various efficiencies to deiminate filaggrin and particular calcium and pH sensitivities. Immunoelectron microscopy demonstrated that PAD1 and PAD3 are co-located with filaggrin within the filamentous matrix of the deeper corneocytes where the protein is deiminated. This result strongly suggests that both isoforms are involved in the deimination of filaggrin, an essential step leading to free amino acid production necessary for epidermal barrier function. Moreover, PAD1 was shown to persist up to the upper corneocytes where it deiminates keratin K1, a modification supposed to be related to ultrastructural changes of the matrix.