Proteomic Analysis of Loricrin Knockout Mouse Epidermis.
Proteomic Analysis of Loricrin Knockout Mouse Epidermis.
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DOI：
10.1021/acs.jproteome.6b00108
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发表时间：
2016-07
影响因子：
4.4
通讯作者：
R. Rice;B. Durbin-Johnson;Y. Ishitsuka;M. Salemi;B. Phinney;David M. Rocke;D. Roop
中科院分区：
文献类型：
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作者：
R. Rice;B. Durbin-Johnson;Y. Ishitsuka;M. Salemi;B. Phinney;David M. Rocke;D. Roop
哺乳动物表皮角质细胞的交联包膜充当表皮脂质屏障组装的支架。因此，角质形成细胞转谷氨酰胺酶（TGM1）导致的包膜交联缺陷是导致以屏障缺陷为特征的人类常染色体隐性先天性鱼鳞病的主要原因。一些包膜蛋白成分的丢失也会导致鱼鳞病表型的预期很难得到证实。为了帮助合理化这一观察结果，我们将 loricrin 敲除小鼠的表皮蛋白质谱与野生型进行了比较。尽管敲除的表型较温和，但与野生型相比，约 40 种蛋白质并入包膜材料的程度显着不同。近一半也以类似改变的程度并入角质细胞的二硫键连接的角蛋白网络中。结果表明，由于细胞成熟过程中蛋白质-蛋白质相互作用，兜甲蛋白的损失改变了它们与包膜的结合。质谱蛋白质分析显示，角蛋白 1、角蛋白 10 和兜甲蛋白是主要的包膜成分，并且还有数十种其他蛋白质也是成分。尽管由于许多替代转谷氨酰胺酶底物的可用性而损失了单一成分，这一发现有助于合理化功能性包膜的潜在形成。
The crosslinked envelope of the mammalian epidermal corneocyte serves as a scaffold for assembly of the lipid barrier of the epidermis. Thus, deficient envelope crosslinking by keratinocyte transglutaminase (TGM1) is a major cause of the human autosomal recessive congenital ichthyoses characterized by barrier defects. Expectations that loss of some envelope protein components would also confer an ichthyosis phenotype have been difficult to demonstrate. To help rationalize this observation, the protein profile of epidermis from loricrin knockout mice has been compared to that of wild type. Despite the mild phenotype of the knockout, some 40 proteins were incorporated into envelope material to significantly different extents compared to those of wild type. Nearly half were also incorporated to similarly altered extents into the disulfide bonded keratin network of the corneocyte. The results suggest that loss of loricrin alters their incorporation into envelopes as a consequence of protein-protein interactions during cell maturation. Mass spectrometric protein profiling revealed that keratin 1, keratin 10, and loricrin are prominent envelope components and that dozens of other proteins are also components. This finding helps rationalize the potential formation of functional envelopes, despite loss of a single component, due to the availability of many alternative transglutaminase substrates.