Hornerin, a novel profilaggrin-like protein and differentiation-specific marker isolated from mouse skin
Hornerin, a novel profilaggrin-like protein and differentiation-specific marker isolated from mouse skin
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DOI：
10.1074/jbc.m107512200
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发表时间：
2001-12-14
影响因子：
4.8
通讯作者：
Huh, NH
中科院分区：
文献类型：
--
作者：
Makino, T;Takaishi, M;Huh, NH
通过应用于发育中的小鼠皮肤的RNA差异显示，分离出一种名为hornerin的新型小鼠cDNA。 Hornerin 具有 2,496 个氨基酸，在 N 末端包含 EF-hand 结构域，后面是间隔序列和大的重复结构域，表明 Hornerin 是“融合基因”型角化包膜前体蛋白家族的新成员。发现霍纳蛋白的重复结构域富含甘氨酸、丝氨酸和谷氨酰胺。 Hornerin 在所检查的成年小鼠组织中的舌头、食道、前胃和皮肤中表达，所有这些组织都是角化复层上皮。在胚胎小鼠皮肤中，在妊娠第15.5天，在表皮中首次检测到hornerin mRNA，同时伴随着颗粒层的形成。据此，在成熟表皮的颗粒层和角化层中检测到了hornerin。在表皮的颗粒细胞中，在透明角质蛋白颗粒中检测到了霍纳蛋白以及聚丝蛋白原。此外，小鼠皮肤的蛋白质印迹分析表明，hornerin 蛋白在表皮分化过程中被切割，表明可能存在翻译后蛋白水解加工，如在聚丝蛋白原中观察到的那样。用 0.12 mm Ca2+ 诱导原代小鼠表皮角质形成细胞分化，诱导霍纳蛋白的产生。这些结果表明，hornerin 在结构和功能上与家族成员中的聚丝蛋白原最相似，并且可能发挥多效性作用，包括在角化中的作用。
A novel mouse cDNA named hornerin was isolated by RNA differential display applied to developing mouse skin. Hornerin, which has 2,496 amino acids, comprises EF-hand domains at the N terminus followed by a spacer sequence and a large repetitive domain, indicating that hornerin is a novel member of the "fused gene"-type cornified envelope precursor protein family. The repetitive domain of hornerin was found to be rich in glycine, serine, and glutamine. Hornerin was expressed in the tongue, esophagus, forestomach, and skin among the adult mouse tissues examined, all of them cornifying stratified epithelium. In the embryonic mouse skin, hornerin mRNA was first detected on gestational day 15.5 in the epidermis coincidentally with the formation of a granular layer. In accordance with this, hornerin was detected in the granular and cornified layers of the mature epidermis. In the granular cells of the epidermis, the hornerin protein was detected in keratohyalin granules together with profilaggrin. Furthermore, Western blot analysis of the mouse skin showed that the hornerin protein was cleaved during the process of epidermal differentiation, indicating possible posttranslational proteolytic processing as is observed in profilaggrin. Differentiation of primary mouse epidermal keratinocytes with 0.12 mm Ca2+ resulted in the induction of hornerin. These results indicate that hornerin is structurally as well as functionally most similar to profilaggrin among the family members and possibly plays pleiotropic roles, including a role in cornification.