Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and-3
Separation force measurements reveal different types of modulation of E-cadherin-based adhesion by nectin-1 and-3
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DOI：
10.1074/jbc.m412544200
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发表时间：
2005-02-11
影响因子：
4.8
通讯作者：
Dufour, S
中科院分区：
文献类型：
--
作者：
Martinez-Rico, C;Pincet, F;Dufour, S
Nectin 是在基于钙粘蛋白的粘附连接处发现的不依赖 Ca2+ 的细胞粘附分子。我们使用双移液管测定法来测量分离细胞双联体所需的力，以确定连接蛋白如何影响细胞-细胞粘附的形成和强度。分离表达 nectin-1 或 nectin-3 的 L 细胞双联体所需的力比分离表达 E-钙粘蛋白的细胞双联体所需的力更小。表达nectin-1或nectin-3的细胞之间形成的异二聚体比同二聚体粘附得更牢固。 Nectin-3 不与 nectin-1 反式相互作用，抑制 E-钙粘蛋白介导的粘附。然而，当nectin-1的胞外片段与细胞中高水平表达的nectin-3反式相互作用时，它对E-钙粘蛋白依赖性细胞粘附不具有激动作用。相比之下，当nectin-3的细胞外片段与细胞中低水平表达的内源性nectin-1相互作用时，它对基于钙粘蛋白的粘附具有显着的激动作用。我们的结果表明，E-钙粘蛋白是参与细胞粘附的关键分子，并且涉及细胞nectin-1与nectin-3反式相互作用的基于E-钙粘蛋白的粘附的调节与涉及细胞nectin-3与nectin-1反式相互作用的调节有本质上的不同，并且取决于细胞表达的nectin水平。
Nectins are Ca2+-independent cell adhesion molecules found at cadherin-based adherens junctions. We used a,dual pipette assay that measures the forces required to separate cell doublets to determine how nectins affect the formation and strength of cell-cell adhesion. Less force was required to separate doublets of L cells expressing nectin-1 or nectin-3 than to separate doublets of E-cadherin-expressing cells. Heterodimers formed between cells expressing nectin-1 or nectin-3 adhered more strongly than homodimers. Nectin-3 that does not trans-interact with nectin-1 inhibited E-cadherin-mediated adhesion. However, the extracellular fragment of nectin-1 did not have an agonistic effect on E-cadherindependent cell adhesion when it trans-interacted with nectin-3, expressed at high levels in cells. In contrast, the extracellular fragment of nectin-3 had a significant agonistic effect on cadherin-based adhesion when it interacted with endogenous nectin-1, expressed at low levels in cells. Our results indicate that E-cadherin is the key molecule involved in cell adhesion and that the regulation of E-cadherin-based adhesion involving cellular nectin-1 trans-interacting with nectin-3 is qualitatively different from that involving cellular nectin-3 trans-interacting with nectin-1 and depends on the nectin levels expressed by cells.