Expression of functionally distinct variants of the beta(4)A integrin subunit in relation to the differentiation state in human intestinal cells.
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 alpha(6)beta(4), which is thought to be ubiquitously expressed by intestinal cells. However, in this study, a re-evaluation of the beta(4) subunit expression with different antibodies revealed that two forms of beta(4) exist in the human intestinal epithelium. Furthermore, we show that differentiated enterocytes express a full-length 205-kDa beta(4)A subunit, whereas undifferentiated crypt cells express a novel beta(4)A subunit that does not contain 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 splicing. Moreover, we found that these two beta(4)A forms can associate into alpha(6)beta(4)A complexes; however, the beta(4)A(ctd-) integrin expressed by the undifferentiated crypt cells is not functional for adhesion to laminin-5. Hence, these studies identify a novel alpha(6)beta(4)A(ctd-) integrin expressed in undifferentiated intestinal crypt cells that is functionally distinct.
Basora
N
N
Centre de Recherche en Biologie du Développement des Epitheliums et Thématique de Physiopathologie Digestive du Centre de Recherche Clinique du CUSE, Quebec, Canada.
Herring-Gillam
F E
FE
Boudreau
F
F
Perreault
N
N
Pageot
L P
LP
Simoneau
M
M
Bouatrouss
Y
Y
Beaulieu
J F
JF
D000328:Adult; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D017931:DNA Primers; D006801:Humans; D039663:Integrin beta4; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D017931:DNA Primers; D039663:Integrin beta4