The structural analysis of adhesions mediated by Ep-CAM
The structural analysis of adhesions mediated by Ep-CAM
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DOI：
10.1006/excr.1998.4263
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发表时间：
1999-01-10
影响因子：
3.7
通讯作者：
Litvinov, SV
中科院分区：
文献类型：
--
作者：
Balzar, M;Prins, FA;Litvinov, SV
上皮细胞粘附分子Ep-CAM能够介导Ca 2+非依赖性的同型细胞-细胞粘附，当被引入缺乏其自身的细胞-细胞相互作用手段的细胞中时。我们使用（共聚焦）免疫荧光和（免疫）电子显微镜研究Ep-CAM介导的粘连的结构组织及其与其他类型的细胞间粘连的关系。分析了Ep-CAM转染的细胞系、上皮来源的细胞和上皮组织。在转染的L细胞中，Ep-CAM使相对的细胞间膜在零星接触时紧密接近（约10-14 nm）;然而，没有观察到类似于连接复合物的结构。在用Ep-CAM和E-钙粘蛋白共转染的L细胞中，这两种分子都定位在细胞与细胞接触的位点，形成独立的粘附位点，在结构可区分的钙粘蛋白介导的粘附连接中检测不到Ep-CAM。在分化良好的癌细胞系Ep-CAM共定位与E-钙粘蛋白几乎沿着整个横向域，然而，没有共定位之间的Ep-CAM和紧密连接复合物（occludin和ZO-1），桥粒（桥斑蛋白I/II），或细胞基质粘附（β 1整联蛋白）的组成部分观察。这通过分析正常结肠的极化上皮证实，其中Ep-CAM存在于包括粘附连接区域的侧膜处，但完全排除在顶细胞膜（微绒毛）、紧密连接和桥粒之外。我们得出结论：（1）Ep-CAM在L细胞中不形成连接复合物，（2）在上皮细胞中，细胞表面Ep-CAM存在于侧细胞膜上，但被排除在紧密连接和桥粒之外，（3）在上皮细胞中，Ep-CAM存在于由经典钙粘蛋白（特别是E-cadherin）介导的粘附中，两种类型的分子保持为独立的簇。Ep-CAM与钙粘蛋白的共定位可能是Ep-CAM调节钙粘蛋白介导的粘连的重要机制。(C)北京：科学出版社.
The epithelial cell adhesion molecule Ep-CAM is capable of mediating Ca2+-independent homotypic cell-cell adhesion when introduced into cells lacking their own means of cell-cell interactions. We used (confocal) immunofluorescent and (immuno-) electron microscopy to investigate the structural organization of Ep-CAM-mediated adhesions and their relation to other types of intercellular adhesions. Ep-CAM-transfected cell lines, cells of epithelial origin, and epithelial tissues were analyzed. In transfected L cells Ep-CAM brings the opposing intercellular membranes into a close proximity (approximately 10-14 nm) at sporadic contacts; however, no structures resembling junctional complexes were observed. In L cells cotransfected with Ep-CAM and E-cadherin, both molecules localize at the sites of cell-cell contact, forming independent adhesion sites with no Ep-CAM detectable within the structurally distinguishable cadherin-mediated adherens junctions. In well-differentiated carcinoma cell lines Ep-CAM colocalized with E-cadherin practically along the whole lateral domain; however, no colocalization was observed between Ep-CAM and the components of the tight junction complex (occludin and ZO-1), desmosomes (desmoplakins I/II), or cell-substrate adhesions (beta 1 integrins). This was confirmed by analysis of polarized epithelium of normal colon where Ep-CAM was present at the lateral membrane including the adherens junction areas, but was fully excluded from the apical cell membrane (microvilli), tight junctions, and desmosomes. We conclude that (1) Ep-CAM does not form junctional complexes in L cells, (2) in epithelial cells, cell surface Ep-CAM is present at the lateral cell membrane, but is excluded from tight junctions and desmosomes, and (3) in epithelial cells, Ep-CAM is present within adhesions mediated by the classic cadherins (especially E-cadherin) with both types of molecules remaining as independent clusters. The colocalization with cadherins might be important for the modulating effect of Ep-CAM on cadherin-mediated adhesions. (C) 1999 Academic Press.