ASPECTS OF CADHERIN/CATENIN COMPLEXES

Cells of epithelial tissues display tight intercellular interactions which
are mediated by a variety of cellular structures including adherens
junctions, desmosomes, gap junctions and tight junctions. These cell-cell
associations are not only important in the formation of a tissue but are
equally important in maintaining its integrity throughout the life of the
organism. A family of proteins, termed cadherins has been shown to mediate calcium-
dependent cell adhesion. Cadherin expression is developmentally regulated
and correlates with morphogenetic events suggesting that these adhesion
molecules are essential to normal development. In addition, it has been
suggested that down-regulation of cadherin or cadherin function may
contribute to the metastatic spread of carcinomas. Cadherins have highly
conserved cytoplasmic domains that interact indirectly with the
cytoskeleton. This interaction is essential for the cadherin to mediate
adhesion. Several proteins, termed catenins, have been identified that are
associated with the cadherins. The catenins are thought to 1) mediate
cytoskeletal interactions with the cadherins, thus linking the
cytoskeleton to the plasma membrane and 2) regulate adhesive activity of
the cadherins. The goals of this project are to further our understanding of the roles of
cadherins and the catenins in the interaction of cells with one another
and to determine how the cadherin/catenin complex relates to the structure
we know as an adherens junction. The specific aims of this project are 1) to determine which domains of the
catenins are necessary for association with the complex, 2) to
characterize cadherin-mediated adhesion in cells that express more than
one cadherin; 3) to look at cadherin/catenin complexes in cells that do
not form typical complexes such as fibroblasts; and 4) to determine if
beta- and gamma-catenin can substitute for one another in a cadherin
complex. We will accomplish these aims by the use of molecular biological
techniques to produce truncated versions of the various proteins; by using
antibodies to inhibit function of the various proteins; and with
ultrastructural analysis of junctional complexes.