Cleavage of desmoglein 3 can explain its depletion from keratinocytes in pemphigus vulgaris
Cleavage of desmoglein 3 can explain its depletion from keratinocytes in pemphigus vulgaris
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DOI：
10.1111/j.1600-0625.2008.00719.x
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发表时间：
2008-10-01
影响因子：
3.6
通讯作者：
Lanza, Alessandro
中科院分区：
文献类型：
--
作者：
Cirillo, Nicola;Campisi, Giuseppina;Lanza, Alessandro
我们先前已经证明，寻常天疱疮患者的血清诱导角质形成细胞中桥粒芯糖蛋白3（Dsg 3）半衰期的减少（FEBS Lett 2006：580：3276）。这种现象似乎是由于Dsg3从桥粒中逐渐耗尽而发生的。在这里，我们报告了全长Dsg 3的减少可能是由于其进行性切割，导致形成两种表观分子量约为60 kDa（片段1）和70 kDa（片段2）的片段化产物，如蛋白质印迹所示。出乎意料的是，片段化模式的分析表明裂解发生在细胞内。一致的是，片段1脱落并定位在胞质溶胶中，如活细胞免疫荧光显微镜所示。全长斑珠蛋白和Dsg1的总量明显不变。总之，我们的研究结果提供了证据，Dsg3的蛋白水解加工可以导致Dsg3从细胞中耗尽。
We have previously demonstrated that serum of patients with pemphigus vulgaris induces reduction of desmoglein 3 (Dsg3) half-life in keratinocytes (FEBS Lett 2006: 580: 3276). This phenomenon seems to occur as a consequence of the progressive depletion of Dsg3 from desmosomes. Here we reported that reduction of full-length Dsg3 may be due to its progressive cleavage, leading to the formation of two fragmentation products with apparent molecular masses of about 60 kDa (fragment 1) and 70 kDa (fragment 2), as revealed by Western blotting. Unexpectedly, analysis of fragmentation pattern suggested cleavage to occur intracellularly. Consistently, fragment 1 was shed and localized within the cytosol, as shown by living cell immunofluorescence microscopy. Total amounts of full-length plakoglobin and Dsg1 were apparently unchanged. Taken together, our findings provide evidence that proteolytic processing of Dsg3 can lead to depletion of Dsg3 from the cell.