Expression of functionally distinct variants of the beta(4)A integrin subunit in relation to the differentiation state in human intestinal cell

Integrins are important mediators of cell-laminin interactions. In the smal l intestinal epithelium, which consists of spatially separated proliferativ e and differentiated cell populations located, respectively, in the crypt a nd on the villus, laminins and laminin-binding; integrins are differentiall y expressed along the cryptvillus axis. One exception to this is the integr in alpha(6)beta(4), which is thought to be ubiquitously expressed by intest inal cells. However, in this study, a re-evaluation of the beta(4) subunit expression with different antibodies revealed that two forms of beta(4) exi st in the human intestinal epithelium. Furthermore, we show that differenti ated enterocytes express a full-length 205-kDa beta(4)A subunit, whereas un differentiated crypt cells express a novel beta(4)A subunit that does not c ontain the COOH-terminal segment of the cytoplasmic domain (beta(4)A(ctd-)) . This new form was not found to arise from alternative beta(4) mRNA splici ng. Moreover, we found that these two beta(4)A forms can associate into alp ha(6)beta(4)A complexes; however, the beta 4A(ctd-) integrin expressed by t he undifferentiated crypt cells is not functional for adhesion to laminin-5 . Hence, these studies identify a novel alpha(6)beta(4)A(ctd-) integrin exp ressed in undifferentiated intestinal crypt cells that is functionally dist inct.