The dystroglycans (-DG and -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 demonstrate that the DG complex, composed of -DG, -DG and utrophin, is specifically expressed in the basolateral membrane of Caco2-BBE monolayer. The DG complex co-precipitated with 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 1 integrin and laminin-1, whereas activation of DG receptors by laminin-2 reduced the interaction between 1 integrin and laminin-2. Finally, we demonstrate that the intracellular C-terminal tail of -DG and its binding to the DG binding domain of utrophin are crucial for the interactions between laminin-1/-2 and 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.