Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins.
For the extracellular (EC) domain of E-cadherin to function in homophilic adhesion it is thought that its intracytoplasmic (IC) domain must bind alpha- and beta-catenins, which link it to the actin cytoskeleton. However, the IC domain of pemphigus vulgaris antigen (PVA or Dsg3), which is in the desmoglein subfamily of the cadherin gene superfamily, does not bind alpha- or beta-catenins. Because desmogleins have also been predicted to function in the cell adhesion of desmosomes, we speculated that the PVA IC domain might be able to act in a novel way in conferring adhesive function on the EC domain of cadherins. To test this hypothesis we studied aggregation of mouse fibroblast L cell clones that expressed chimeric cDNAs encoding the EC domain of E-cadherin with various IC domains. We show here that the full IC domain of PVA as well as an IC subdomain containing only 40 amino acids of the PVA intracellular anchor (IA) region confer adhesive function on the E-cadherin EC domain without catenin-like associations with cytoplasmic molecules or fractionation with the cell cytoskeleton. This IA region subdomain is evolutionarily conserved in desmogleins, but not classical cadherins. These findings suggest an important cell biologic function for the IA region of desmogleins and demonstrate that strong cytoplasmic interactions are not absolutely necessary for E-cadherin-mediated adhesion.
Roh
J Y
JY
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Stanley
J R
JR
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; C495300:Dsg3 protein, mouse; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin