CHARACTERIZATION OF CADHERIN-4 AND CADHERIN-5 REVEALS NEW ASPECTS OF CADHERINS

Several properties of cadherin-4 and cadherin-5 were characterized by using the cDNA transfection approach. The proteins of both cadherins h ad a relative molecular mass of about 130 kDa and were present at the cell periphery, especially at cell-cell contact sites. These cadherins were easily digested with trypsin, and Ca2+ protected cadherin-4, but not cadherin-5, from the digestion. In immunoprecipitation, cadherin- 4 co-precipitated with two major proteins of 105 kDa and 95 kDa, respe ctively. The 105 kDa and the 95 kDa proteins are likely to correspond to alpha- and beta-catenins. Cadherin-5 co-precipitated with only one major protein of 95 kDa, but seems to associate with the 105 kDa prote in. On the other hand, plakoglobin or gamma-catenin did not co-precipi tate well with either cadherin-4 or cadherin-5 in immunoprecipitation, but plakoglobin also appears to associate weakly with these cadherins . Cadherin-4 transfectants aggregated within 30 minutes in a cell aggr egation assay, but cadherin-5 transfectants did not aggregate under th e same conditions. Furthermore, the transfectants of chimeric cadherin -4 with cadherin-5 cytoplasmic domain showed cell aggregation activity comparable to that of wildtype cadherin-4 transfectants, whereas the transfectants of chimeric cadherin-5 with cadherin-4 cytoplasmic domai n did not show appreciable cell aggregation, suggesting that the extra cellular domains of cadherins, in conjunction with their cytoplasmic d omains, play an important role in cell aggregation activity. These res ults show that cadherin-4 is very similar to the classical cadherins, whereas cadherin-5 is functionally as well as structurally distinct fr om classical cadherins.