J Biol Chem, Vol. 274, Issue 42, 29819-29825, October 15, 1999

Expression of Functionally Distinct Variants of the ₄A Integrin Subunit in Relation to the Differentiation State in Human Intestinal Cells

From the Centre de Recherche en Biologie du Développement des Épitheliums et Thématique de Physiopathologie Digestive du Centre de Recherche Clinique du CUSE, Département d'anatomie et de biologie cellulaire, Faculté de médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4

Integrins are important mediators of cell-laminin interactions. In the small intestinal epithelium, which consists of spatially separated proliferative and differentiated cell populations located, respectively, in the crypt and on the villus, laminins and laminin-binding integrins are differentially expressed along the crypt-villus axis. One exception to this is the integrin ₆₄, which is thought to be ubiquitously expressed by intestinal cells. However, in this study, a re-evaluation of the ₄ subunit expression with different antibodies revealed that two forms of ₄ exist in the human intestinal epithelium. Furthermore, we show that differentiated enterocytes express a full-length 205-kDa ₄A subunit, whereas undifferentiated crypt cells express a novel ₄A subunit that does not contain the COOH-terminal segment of the cytoplasmic domain (₄A_ctd). This new form was not found to arise from alternative ₄ mRNA splicing. Moreover, we found that these two ₄A forms can associate into ₆₄A complexes; however, the ₄A_ctd integrin expressed by the undifferentiated crypt cells is not functional for adhesion to laminin-5. Hence, these studies identify a novel ₆₄A_ctd integrin expressed in undifferentiated intestinal crypt cells that is functionally distinct.