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Am J Physiol Gastrointest Liver Physiol 290: G1228-G1242, 2006. First published December 15, 2005; doi:10.1152/ajpgi.00378.2005
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MUCOSAL BIOLOGY

Dystroglycan receptor is involved in integrin activation in intestinal epithelia

Adel Driss, Laetitia Charrier, Yutao Yan, Vivienne Nduati, Shanthi Sitaraman, and Didier Merlin

Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia

Submitted 15 August 2005 ; accepted in final form 8 December 2005

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 beta1-integrin, suggesting a possible interaction among these proteins. In addition, we observed that activation of DG receptors by laminin-1 enhanced the interaction between beta1-integrin and laminin-1, whereas activation of DG receptors by laminin-2 reduced the interaction between beta1-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 beta1-integrin. Collectively, these novel results indicate that dystroglycans play important roles in the regulation of interactions between intestinal epithelial cells and the extracellular matrix.

laminin; beta1-integrin; Caco-2-BBE; electric cell-substrate impedance sensing



Address for reprint requests and other correspondence: D. Merlin, Dept. of Medicine, Division of Digestive Diseases, Emory Univ., 615 Michael St., Atlanta, GA 30322 (e-mail: dmerlin{at}emory.edu)




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