Ozawa M, Kemler R
Department of Biochemistry, Faculty of Medicine, Kagoshima University, Kagoshima 890-8520, Japan.
J Cell Biol. 1998 Sep 21;142(6):1605-13. doi: 10.1083/jcb.142.6.1605.
Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Deletion of the COOH-terminal residues of the E-cadherin cytoplasmic domain has been shown to abolish its cell adhesive activity, which has been ascribed to the failure of the deletion mutants to associate with catenins. Based on our present results, this concept needs revision. As was reported previously, leukemia cells (K562) expressing E-cadherin with COOH-terminal deletion of 37 or 71 amino acid residues showed almost no aggregation. Cells expressing E-cadherin with further deletion of 144 or 151 amino acid residues, which eliminates the membrane-proximal region of the cytoplasmic domain, showed E-cadherin-dependent aggregation. Thus, deletion of the membrane-proximal region results in activation of the nonfunctional E-cadherin polypeptides. However, these cells did not show compaction. Chemical cross-linking revealed that the activated E-cadherin polypeptides can be cross-linked to a dimer on the surface of cells, whereas the inactive polypeptides, as well as the wild-type E-cadherin polypeptide containing the membrane-proximal region, can not. Therefore, the membrane-proximal region participates in regulation of the adhesive activity by preventing lateral dimerization of the extracellular domain.
钙黏着蛋白是参与钙离子依赖的细胞间黏附的跨膜糖蛋白。E-钙黏着蛋白细胞质结构域羧基末端残基的缺失已被证明会消除其细胞黏附活性，这归因于缺失突变体无法与连环蛋白结合。基于我们目前的结果，这一概念需要修正。如先前报道，表达羧基末端缺失37或71个氨基酸残基的E-钙黏着蛋白的白血病细胞（K562）几乎不发生聚集。表达进一步缺失144或151个氨基酸残基（消除细胞质结构域的膜近端区域）的E-钙黏着蛋白的细胞表现出E-钙黏着蛋白依赖性聚集。因此，膜近端区域的缺失导致无功能的E-钙黏着蛋白多肽激活。然而，这些细胞并未表现出紧密化。化学交联显示，活化的E-钙黏着蛋白多肽可在细胞表面交联形成二聚体，而无活性的多肽以及含有膜近端区域的野生型E-钙黏着蛋白多肽则不能。因此，膜近端区域通过阻止细胞外结构域的侧向二聚化参与黏附活性的调节。
