Nonchordate classic cadherins have a structurally and functionally unique domain that is absent from chordate classic cadherins

Nonchordate classic cadherins have a structurally and functionally unique domain that is absent from chordate classic cadherins
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DOI:
10.1006/dbio.1999.9494
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发表时间:
1999-12-01
影响因子:
2.7
通讯作者:
Tsukita, S
Tsukita, S
中科院分区:
生物学3区
文献类型:
--
作者:
Oda, H;Tsukita, S

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经典的钙粘蛋白是细胞与细胞粘附连接中的粘附分子,对动物体的构建有很大的贡献。它们的分子结构在脊索动物和非脊索动物后生动物之间显示出明显的差异。尽管非脊索动物经典钙粘蛋白具有钙粘蛋白超家族特异性的细胞外重复序列 (CR) 和高度保守的细胞质结构域 (CP),但这些钙粘蛋白具有脊椎动物和海鞘经典钙粘蛋白所不具备的独特的细胞外结构域。我们将其称为原始经典钙粘蛋白结构域 (PCCD)。为了了解 PCCD 的作用,我们构建并表征了果蝇经典钙粘蛋白 DE-钙粘蛋白的一系列突变形式。生化分析表明最后两个CR与PCCD形成特殊的蛋白水解结构。 PCCD的突变并没有消除培养细胞中DE-钙粘蛋白的细胞与细胞结合功能,但阻止了钙粘蛋白有效地转位到发育胚胎的上皮细胞的质膜上。此外,基因救援试验表明,虽然 CP 介导的控制在气管融合中发挥核心作用,但 PCCD 在将 DE-钙粘蛋白有效招募到质膜顶端区域方面的作用对于动态上皮形态发生也很重要。我们认为脊索动物和非脊索动物后生动物之间经典钙粘蛋白介导的细胞间粘附模式存在根本差异。 (C) 1999,学术出版社。
Classic cadherins, which are adhesion molecules in cell-cell adherens junctions, have a large contribution to the construction of the animal body. Their molecular structures show clear differences between chordate and nonchordate metazoans. Although nonchordate classic cadherins have cadherin superfamily-specific extracellular repeats (CRs) and a highly conserved cytoplasmic domain (CP), these cadherins have a unique extracellular domain that is absent from vertebrate and ascidian classic cadherins. We called this the primitive classic cadherin domain (PCCD). To understand the roles of the PCCD, we constructed and characterized a series of mutant forms of the Drosophila classic cadherin DE-cadherin. Biochemical analyses indicated that the last two CRs and PCCD form a special structure with proteolytic cleavage. Mutations in the PCCD did not eliminate the cell-cell-binding function of DE-cadherin in cultured cells, but prevented the cadherin from efficiently translocating to the plasma membrane in epithelial cells of the developing embryo. In addition, genetic rescue assays suggested that although CP-mediated control plays a central role in tracheal fusion, the role of the PCCD in efficient recruitment of DE-cadherin to apical areas of the plasma membranes is also important for dynamic epithelial morphogenesis. We propose that there is a fundamental difference in the mode of classic cadherin-mediated cell-cell adhesion between chordate and nonchordate metazoans. (C) 1999, Academic Press.