Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds.
Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino-terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces.
Zhou
H
H
McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
Fuks
A
A
Alcaraz
G
G
Bolling
T J
TJ
Stanners
C P
CP
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D016466:CHO Cells; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D014162:Transfection
D002272:Carcinoembryonic Antigen; D015816:Cell Adhesion Molecules, Neuronal; D010455:Peptides; D011993:Recombinant Fusion Proteins