Prozialeck Walter C, Fay Michael J, Lamar Peter C, Pearson Celeste A, Sigar Ira, Ramsey Kyle H
Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois 60515, USA.
Infect Immun. 2002 May;70(5):2605-13. doi: 10.1128/IAI.70.5.2605-2613.2002.
The cadherin/catenin complex serves as an important structural component of adherens junctions in epithelial cells. Under certain conditions, beta-catenin can be released from this complex and interact with transcription factors in the nucleus to stimulate the expression of genes that regulate apoptosis and cell cycle control. While studying the effects of the bacterial pathogen Chlamydia trachomatis on human cervical epithelial cells in culture, we observed that C. trachomatis caused the epithelial cells to separate from each other without detaching from their growing surface. The objective of the present study was to determine if this effect might involve the disruption of the cadherin/catenin complex. Primary cultures of human cervical epithelial cells or HeLa cells were infected with C. trachomatis serovar E. Cadherin-like immunoreactive materials and beta-catenin were visualized by immunofluorescence. Preliminary studies showed that N-cadherin was the primary cadherin expressed in both the primary cultures and the HeLa cells. In noninfected cells, N-cadherin and beta-catenin were colocalized at the intercellular junctional complexes. By contrast, the infected cells showed a marked loss of both N-cadherin and beta-catenin labeling from the junctional complexes and the concomitant appearance of intense beta-catenin labeling associated with the chlamydial inclusion. The results of Western blot analyses of extracts of C. trachomatis showed no evidence of cross-reactivity with the beta-catenin antibody. These results indicate that C. trachomatis causes the breakdown of the N-cadherin/beta-catenin complex and that the organism can sequester beta-catenin within the chlamydial inclusion. This could represent an important mechanism by which C. trachomatis alters epithelial cell function.
钙黏蛋白/连环蛋白复合体是上皮细胞黏附连接的重要结构成分。在某些情况下，β-连环蛋白可从该复合体中释放出来，并与细胞核中的转录因子相互作用，以刺激调节细胞凋亡和细胞周期控制的基因表达。在研究细菌病原体沙眼衣原体对培养的人宫颈上皮细胞的影响时，我们观察到沙眼衣原体导致上皮细胞彼此分离，但并未从其生长表面脱离。本研究的目的是确定这种效应是否可能涉及钙黏蛋白/连环蛋白复合体的破坏。用人宫颈上皮细胞或HeLa细胞的原代培养物感染沙眼衣原体血清型E。通过免疫荧光观察钙黏蛋白样免疫反应性物质和β-连环蛋白。初步研究表明，N-钙黏蛋白是原代培养物和HeLa细胞中表达的主要钙黏蛋白。在未感染的细胞中，N-钙黏蛋白和β-连环蛋白共定位于细胞间连接复合体。相比之下，感染的细胞在连接复合体处显示出N-钙黏蛋白和β-连环蛋白标记的明显丧失，同时出现与衣原体包涵体相关的强烈β-连环蛋白标记。沙眼衣原体提取物的蛋白质印迹分析结果显示，没有与β-连环蛋白抗体交叉反应的证据。这些结果表明，沙眼衣原体导致N-钙黏蛋白/β-连环蛋白复合体的分解，并且该生物体可以将β-连环蛋白隔离在衣原体包涵体内。这可能代表沙眼衣原体改变上皮细胞功能的一种重要机制。
