Desmosomes and Extradesmosomal Adhesive Signaling Contacts in Pemphigus
Desmosomes and Extradesmosomal Adhesive Signaling Contacts in Pemphigus
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DOI：
10.1002/med.21310
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发表时间：
2014-11-01
影响因子：
13.3
通讯作者：
Spindler, Volker
中科院分区：
文献类型：
--
作者：
Waschke, Jens;Spindler, Volker
桥粒是存在于所有简单和复杂上皮细胞中的粘连连接。它们在承受广泛机械应力的组织细胞中含量最高，如角质形成细胞和心肌细胞。桥粒的核心是由桥粒钙粘蛋白组成的，这是一种钙粘附素类型的黏附分子，通过螳螂和Plakin家族的接头蛋白连接到中间丝上。此外，桥粒外还存在桥粒钙粘附素。最近的研究表明，这些分子参与了黏附依赖和黏附非依赖的信号传递，因此具有不同于桥粒中相应分子的黏附特性。桥粒内外桥粒钙粘附素的粘附性受损是水疱性皮肤病天疱疮的原因。自身抗体干扰桥粒钙粘附素的结合，改变细胞内的信号通路，后者是细胞黏附丧失所必需的。在已报道的众多信号分子中，p38MAPK、蛋白激酶C和表皮生长因子受体(EGFR)的活性变化是最相关的。该综述重点介绍了桥粒钙粘附素信号转导的最新数据，以及天疱疮皮肤起泡的相关机制。(C)2014年威利期刊公司。
Desmosomes are adhering junctions present in all cells of simple and complex epithelia. They are most abundant in cells of tissues subjected to extensive mechanical stress such as keratinocytes and cardiomyocytes. The core of desmosomes is built up of desmosomal cadherins, cadherin-type adhesion molecules that are tethered to intermediate filaments via adaptor proteins of the armadillo and the plakin family. In addition, desmosomal cadherins are present outside of desmosomes. Recent investigations indicate that these molecules are involved in adhesion-dependent and adhesion-independent signaling and thus have functions different from the adhesive properties of their counterparts within desmosomes. Impaired adhesion of desmosomal cadherins both within and outside of desmosomes is the cause of the blistering skin disease pemphigus. Autoantibodies interfere with the binding of desmosomal cadherins and alter intracellular signaling pathways, the latter of which is necessary for loss of cell adhesion. Among the plethora of signaling molecules reported, altered activities of p38MAPK, protein kinase C, and epidermal growth factor receptor (EGFR) are most relevant. This review highlights the recent data on signaling by desmosomal cadherins and the mechanisms involved in pemphigus skin blistering. (C) 2014 Wiley Periodicals, Inc.