The cadherin-catenin complex as a focal point of cell adhesion and signalling: new insights from three-dimensional structures.
Cadherins are a large family of single-pass transmembrane proteins principally involved in Ca2+-dependent homotypic cell adhesion. The cadherin molecules comprise three domains, the intracellular domain, the transmembrane domain and the extracellular domain, and form large complexes with a vast array of binding partners (including cadherin molecules of the same type in homophilic interactions and cellular protein catenins), orchestrating biologically essential extracellular and intracellular signalling processes. While current, contrasting models for classic cadherin homophilic interaction involve varying numbers of specific repeats found in the extracellular domain, the structure of the domain itself clearly remains the main determinant of cell stability and binding specificity. Through intracellular interactions, cadherin enhances its adhesive properties binding the cytoskeleton via cytoplasmic associated factors alpha- catenin, beta-catenin and p120ctn. Recent structural studies on classic cadherins and these catenin molecules have provided new insight into the essential mechanisms underlying cadherin-mediated cell interaction and catenin-mediated cellular signalling. Remarkable structural diversity has been observed in beta-catenin recognition of other cellular factors including APC, Tcf and ICAT, proteins that contribute to or compete with cadherin/catenin functioning.
Gooding
Jane M
JM
Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Yap
Kyoko L
KL
Ikura
Mitsuhiko
M
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D005810:Multigene Family; D011487:Protein Conformation; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D015534:Trans-Activators; D014157:Transcription Factors; D051178:alpha Catenin; D051176:beta Catenin