DIFFERENTIAL TARGETING OF T-CADHERIN AND N-CADHERIN IN POLARIZED EPITHELIAL-CELLS

To test whether glycosyl phosphatidylinositol-linked T-cadherin is a c omponent of cell junctions like classical cadherins, we have examined its distribution and targeting in polarized epithelial cells. In vivo, T-cadherin was detected on the apical cell surface of the chick intes tinal epithelium. In cultures of transfected Madin-Darby canine kidney cells, T-cadherin was also expressed apically, whereas classical N-ca dherin resided basolaterally, Both cadherins were directly targeted to their respective membrane domains, Mutant proteins were expressed in Madin-Darby canine kidney cells to identify the regions responsible fo r differential cadherin localization. N Delta cyt, an N-cadherin cytop lasmic domain deletion mutant, was stably distributed basolaterally, T his mutant was transported to both the apical and basolateral membrane compartments, followed by preferential removal from the apical surfac e, T-N Delta cyt, a T-cadherin mutant with the N-cadherin cytoplasmic domain deletion, was localized basolaterally, whereas N-T-GPI, a GPI-a nchored N-cadherin mutant, resided at the apical domain, The T-cadheri n carboxyl-terminal 76 amino acids contain the apical targeting signal and include the signal for GPI anchor attachment. Basolateral localiz ation of N-cadherin is achieved through targeting signals in the cytop lasmic domain, Thus, GPI-linked T-cadherin is not a component of cell junctions, consistent with a function as a recognition rather than a c ell adhesion molecule.