Driss Adel, Charrier Laetitia, Yan Yutao, Nduati Vivienne, Sitaraman Shanthi, Merlin Didier
Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, Atlanta, 30322, USA.
Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1228-42. doi: 10.1152/ajpgi.00378.2005. Epub 2005 Dec 15.
The dystroglycans (alpha-DG and beta-DG), which play important roles in the formation of basement membranes, have been well studied in skeletal muscle and nerve, but their expression and localization in intestinal epithelial cells has not been previously investigated. Here, we demonstrated that the DG complex, composed of alpha-DG, beta-DG, and utrophin, is specifically expressed in the basolateral membrane of the Caco-2-BBE monolayer. The DG complex coprecipitated with beta(1)-integrin, suggesting a possible interaction among these proteins. In addition, we observed that activation of DG receptors by laminin-1 enhanced the interaction between beta(1)-integrin and laminin-1, whereas activation of DG receptors by laminin-2 reduced the interaction between beta(1)-integrin and laminin-2. Finally, we demonstrated that the intracellular COOH-terminal tail of beta-DG and its binding to the DG binding domain of utrophin are crucial for the interactions between laminin-1/-2 and beta(1)-integrin. Collectively, these novel results indicate that dystroglycans play important roles in the regulation of interactions between intestinal epithelial cells and the extracellular matrix.
在基底膜形成过程中发挥重要作用的肌营养不良聚糖(α-DG和β-DG),在骨骼肌和神经中已得到充分研究,但此前尚未对其在肠上皮细胞中的表达和定位进行研究。在此,我们证明了由α-DG、β-DG和肌萎缩蛋白组成的DG复合物在Caco-2-BBE单层细胞的基底外侧膜中特异性表达。DG复合物与β(1)整合素共沉淀,提示这些蛋白之间可能存在相互作用。此外,我们观察到层粘连蛋白-1激活DG受体可增强β(1)整合素与层粘连蛋白-1之间的相互作用,而层粘连蛋白-2激活DG受体则会减弱β(1)整合素与层粘连蛋白-2之间的相互作用。最后,我们证明β-DG的细胞内COOH末端尾巴及其与肌萎缩蛋白的DG结合结构域的结合对于层粘连蛋白-1/-2与β(1)整合素之间的相互作用至关重要。总的来说,这些新结果表明肌营养不良聚糖在调节肠上皮细胞与细胞外基质之间的相互作用中发挥重要作用。