Self-contact elimination by membrane fusion.
Self-contact elimination by membrane fusion.
复制标题
通过膜融合消除自接触。
DOI：
10.1073/pnas.1311135110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Yamada,Soichiro
中科院分区：
文献类型：
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作者：
Sumida,GrantM;Yamada,Soichiro
上皮细胞之间相互的、同质的细胞间粘附是上皮屏障功能正确维持所必需的。邻近细胞的相对膜会快速组装连接复合物，而自接触膜却奇怪地不会，这表明细胞具有阻止自连接成熟的能力。使用自接触诱导微加工基底，我们发现正常上皮细胞的自接触通过单个细胞的两个相对质膜之间的膜融合而迅速消除。这种膜融合最常在表达 E-钙粘蛋白的上皮细胞中观察到，但在成纤维细胞中则不然。自接触消除的效率取决于细胞外钙浓度和E-钙粘蛋白的水平，这表明E-钙粘蛋白虽然不是必需的，但通过使相对的膜彼此紧密贴合来增强膜融合效率。此外，Rho 相关蛋白激酶抑制可减少自接触诱导的上皮细胞膜融合，表明这种融合可能通过肌动蛋白-肌球蛋白网络进行机械调节。这种自接触诱导的膜融合是消除不需要的自连接的关键机制，并且可能是细胞自我识别的一个特征。
Mutual, homophilic cell–cell adhesion between epithelial cells is required for proper maintenance of epithelial barrier function. Whereas opposing membranes from neighboring cells rapidly assemble junctional complexes, self-contacting membranes curiously do not, suggesting that cells have the ability to prevent the maturation of self-junctions. Using a self-contact–inducing microfabricated substrate, we show that self-contacts of normal epithelial cells are rapidly eliminated by membrane fusion between two opposing plasma membranes of a single cell. This membrane fusion is most frequently observed in E-cadherin–expressing epithelial cells, but not in fibroblasts. The efficiency of self-contact elimination depends on extracellular calcium concentration and the level of E-cadherin, suggesting that E-cadherin, although not required, enhances membrane fusion efficiency by bringing opposing membranes into close apposition to one another. Additionally, Rho-associated protein kinase inhibition decreases self-contact–induced membrane fusion of epithelial cells, suggesting that this fusion may be mechanically regulated through the actin–myosin network. This self-contact–induced membrane fusion is a key elimination mechanism for unwanted self-junctions and may be a feature of cell self-recognition.