E-cadherin junction formation involves an active kinetic nucleation process
E-cadherin junction formation involves an active kinetic nucleation process
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DOI：
10.1073/pnas.1513775112
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发表时间：
2015-09-01
影响因子：
11.1
通讯作者：
Groves, Jay T.
中科院分区：
文献类型：
--
作者：
Biswas, Kabir H.;Hartman, Kevin L.;Groves, Jay T.
上皮钙粘蛋白介导的细胞-细胞连接在多细胞生物组织结构的发育和维持中起着重要作用。因此，E-钙粘蛋白粘附是提供机械和生化信号输入的细胞微环境的关键要素。在这里，我们报告在活细胞中的天然E-cadherin和E-cadherin（E-cad-ECD）的细胞外结构域之间的连接样结构在体外重建的支持膜。这种混合活细胞支持的膜结构中的连接形成需要活细胞内的活性过程和具有低E-cad-ECD迁移率的支持膜。混合连接招募α-连环蛋白并表现出重塑的皮质肌动蛋白。观察表明，在这个混合系统中的连接形成的初始阶段取决于反式，但不是顺式之间的相互作用的E-钙粘蛋白分子，并通过一个成核过程中，其中突起和收缩的丝状伪足发挥了关键作用。
Epithelial (E)-cadherin-mediated cell-cell junctions play important roles in the development and maintenance of tissue structure in multicellular organisms. E-cadherin adhesion is thus a key element of the cellular microenvironment that provides both mechanical and biochemical signaling inputs. Here, we report in vitro reconstitution of junction-like structures between native E-cadherin in living cells and the extracellular domain of E-cadherin (E-cad-ECD) in a supported membrane. Junction formation in this hybrid live cell-supported membrane configuration requires both active processes within the living cell and a supported membrane with low E-cad-ECD mobility. The hybrid junctions recruit a-catenin and exhibit remodeled cortical actin. Observations suggest that the initial stages of junction formation in this hybrid system depend on the trans but not the cis interactions between E-cadherin molecules, and proceed via a nucleation process in which protrusion and retraction of filopodia play a key role.