Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion
Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion
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DOI：
10.1016/s0925-4773(99)00180-x
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发表时间：
1999-11-01
影响因子：
2.6
通讯作者：
Thesleff, I
中科院分区：
文献类型：
--
作者：
Mikkola, ML;Pispa, J;Thesleff, I
在小鼠Tabby（Ta）突变体和人类X连锁无汗性外胚层发育不良（EDA）综合征中，几种外胚层器官（如毛发、牙齿和汗腺）的发育受损。Tabby和EDA背后的基因已被克隆，并分离出几种替代转录本。该蛋白质产物命名为外胚层发育不良，除了一个短的胶原样序列外，与其他已知基因产物没有明显的功能或显著的同源性。我们已经分离出两种新的Ta转录本，它们是Tabby最长同种型的变体，命名为Ta-A。原位杂交结果显示Ta-A是发育中胚胎的主要转录本。在早期胚胎的内胚层中检测到，随后在神经上皮和外胚层的特定位置检测到。出乎意料的是，Ta的最C-末端结构域的序列分析显示，外胚层发育不良是肿瘤坏死因子（TNF）配体超家族的新成员。小鼠外胚层发育不良的生物化学和功能特点，并显示是一个糖基化，寡聚体II型膜蛋白（N-末端内），典型的肿瘤坏死因子样蛋白的所有特征。TNF家族成员主要参与宿主防御和免疫应答，通常介导细胞凋亡或细胞存活。Ta在几种上皮细胞系中的表达并未导致细胞形态发生显着变化，也不会促进细胞凋亡。相反，它被证明是促进细胞粘附到细胞外基质，其功能与其在上皮-间充质相互作用中调节外胚层附件发育的假定作用一致。外胚层发育不良是第一个已知的上皮形态发生所需的TNF样信号分子。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
In the mouse Tabby (Ta) mutant and human X-linked anhidrotic ectodermal dysplasia (EDA) syndrome development of several ectodermal organs such as hair, teeth, and sweat glands is impaired. The gene behind Tabby and EDA has been cloned, and several alternative transcripts have been isolated. The protein product named ectodysplasin had no obvious function or prominent homology to other known gene products apart from a short collagen-like sequence. We have isolated two novel Ta transcripts which are Variants of the longest isoform of Tabby, named Ta-A. In situ hybridizations revealed Ta-A to be the major transcript in the developing embryo. It was detected in the endoderm of early embryos and subsequently in specific locations in the neuroepithelium and ectoderm. Unexpectedly, sequence analysis of the most C-terminal domain of Ta revealed that ectodysplasin is a novel member of the tumor necrosis factor (TNF) ligand superfamily. Mouse ectodysplasin was biochemically and functionally characterized, and shown to be a glycosylated, oligomeric type II membrane protein (N-terminus inside), all characteristics typical to TNF-like proteins. Members of the TNF family are critically involved in host defence and immune response often mediating either apoptosis or cell survival. Expression of Ta in several epithelial cell lines did not result in prominent changes in cell morphology and did not promote apoptosis. Instead, it was shown to promote cell adhesion to extracellular matrix, a function consistent with its postulated role in epithelial-mesenchymal interactions regulating the development of ectodermal appendages. Ectodysplasin is the first TNF-like signaling molecule described known to be required for epithelial morphogenesis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.