Y receptor-mediated induction of CD63 transcripts, a tetraspanin determined to be necessary for differentiation of the intestinal epithelial cell line, hBRIE 380i cells

Peptide YY (PYY) and neuropeptide Y (NPY) are peptides that coordinate inte stinal activities in response to luminal and neuronal signals. In this stud y, using the rat hybrid small intestinal epithelial cell line, hBRIE 380i c ells, we demonstrated that PYY- and NPY-induced rearrangement of actin fila ments may be in part through a Y1 alpha and/or a nonneuronal Y2 receptor, w hich were cloned from both the intestinal mucosa and the hBRIE 380i cells. A number of PYY/NPY-responsive genes were also identified by subtractive hy bridization of the hBRIE 380i cells in the presence or absence of a 6-h tre atment with PYY. Several of these genes coded for proteins associated with the cell cytoskeleton or extracellular matrix. One of these proteins was th e transmembrane-4 superfamily protein CD63, previously shown to associate w ith beta(1)-integrin and implicated in cell adhesion. CD63 immunoreactivity , using antibody to the extracellular domain, was highest in the differenti ated cell clusters of the hBRIE 380i cells. The hBRIE 380i cells transfecte d with antisense CD63 cDNA lost these differentiated clusters. These studie s suggest a new role for NPY and PYY in modulating differentiation through cytoskeletal associated proteins.