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Dynamic Interplay between Adhesive and Lateral E-Cadherin Dimers

机译:黏着剂和横向E-钙黏着蛋白二聚体之间的动态相互作用

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E-cadherin, an adhesive transmembrane protein of epithelial adherens junctions, forms two types of detergent-resistant dimers: adhesive dimers consisting of cadherin molecules derived from two neighboring cells and lateral dimers incorporating cadherins of the same cell. Both dimers depend on the integrity of the same residue, Trp156. While the relative amounts of these complexes are not certain, we show here that in epithelial A-431 cells, adhesive dimers may be a prevalent form. Inactivation of the calcium-binding sites, located between successive cadherin ectodomains, drastically reduced the amount of adhesive dimers and concomitantly increased the amount of lateral dimers. A similar interdependence of adhesive and lateral dimers was observed in digitonin-permeabilized cells. In these cells, adhesive dimers immediately disassembled after lowering the Ca2+ concentration below 0.1 mM. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime. These observations suggest that cadherin-mediated adhesion is based on the dynamic cycling of E-cadherin between monomeric and adhesive dimer states.
机译:E-钙粘蛋白是上皮粘附连接的粘附性跨膜蛋白,形成两种类型的耐洗涤剂的二聚体:由源自两个相邻细胞的钙粘着蛋白分子组成的粘附二聚体和结合同一细胞的钙粘着蛋白的侧向二聚体。两个二聚体都取决于相同残基Trp 156 的完整性。虽然这些复合物的相对量尚不确定,但我们在这里表明在上皮A-431细胞中,粘性二聚体可能是一种普遍的形式。位于连续的钙粘蛋白胞外域之间的钙结合位点的失活极大地减少了粘合剂二聚体的数量,并随之增加了侧向二聚体的数量。在洋地黄素透化的细胞中观察到相似的黏着剂和侧向二聚体相互依赖性。在这些细胞中,将Ca 2 + 的浓度降低到0.1 mM以下后,粘合剂二聚体立即分解。依赖Trp 156 的侧向二聚体的增加抵消了粘合剂二聚体的消失。将钙浓度增加到正常水平会迅速恢复粘合剂和侧向二聚体之间的原始平衡。我们还提供证据,体内E-钙粘蛋白二聚体的寿命很短。这些观察结果表明钙粘蛋白介导的粘附是基于E-钙粘蛋白在单体和粘附二聚体状态之间的动态循环。

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