Exchange of catenins in cadherin-catenin complex.
beta-Catenin is an intracellular multifunctional protein. In complex with the transmembrane adhesive receptor E-cadherin, it becomes plasma membrane-associated and mediates intercellular adhesion. A cytosolic pool of beta-catenin interacts with DNA-binding proteins and participates in signal transduction. To reveal the possible cross-talk between these two pools, we studied whether beta-catenin is exchanged between its free and cadherin-bound states. We found that pulse-labeled beta-catenin replaces the beta-catenin bound to the cell surface prebiotinylated E-cadherin immediately after synthesis. Approximately 25% of all pulse-labeled beta-catenin destined for E-cadherin associates with this protein via this mechanism. The rest of the newly synthesized beta-catenin arrives at the plasma membrane in a complex with the E-cadherin precursor. Immediately after arrival, this beta-catenin pool is transferred to the prebiotinylated E-cadherin. beta-Catenin released from E-cadherin may participate in new exchange cycles. This beta-catenin exchange is strongly affected in cells that contain mutations in the tumor suppressor gene APC. This process may contribute significantly to both cell-cell adhesion and beta-catenin-dependent signaling.
Klingelhöfer
Jörg
J
Division of Dermatology, Washington University Medical School, St Louis, MO 63110, USA.
Troyanovsky
Regina B
RB
Laur
Oscar Y
OY
Troyanovsky
Sergey
S
D000230:Adenocarcinoma / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D019943:Amino Acid Substitution; D019921:Biotinylation; D001943:Breast Neoplasms / Q000473:pathology; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051180:Desmoplakins; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017491:Genes, APC; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured / 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; D051180:Desmoplakins; D004791:Enzyme Inhibitors; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin