Catenins

Catenins are adapter proteins with multiple binding domains that link the cytoskeleton to cadherins at cell adhesion sites. They bind cadherins, cytoskeletal components, and regulatory proteins, creating a bridge between cell adhesion molecules and the internal cytoskeleton. Different catenins stabilize either actin filaments or intermediate filaments depending on the junction type.

Beta-catenin binds first to the cytosolic domain of cadherin molecules. Alpha-catenin then binds to beta-catenin, and when multiple cadherin-catenin complexes cluster, alpha-catenins dissociate to form cytosolic dimers. These dimers interact strongly with filamentous actin, organizing actin bundles and providing structural strength to adhesion sites.

Plakoglobin and plakophilin establish stable connections between cadherins and intermediate filaments at desmosomes. In contrast, alpha- and beta-catenins dynamically organize the actin cytoskeleton at adherens junctions. These distinct catenin types allow different junction types to connect to different cytoskeletal networks.

P120-catenin tethers to cadherin-catenin complexes and regulates cadherin stability by preventing their endocytosis and promoting cadherin clustering. It also regulates actin polymerization indirectly through Rho GTPases. This stabilization is particularly important at synaptic junctions for maintaining long-term potentiation and synaptic plasticity.

All catenins except alpha-catenin contain a characteristic protein sequence called the armadillo repeat, making them also known as armadillo proteins. This conserved structural domain enables their multiple binding interactions with cadherins and cytoskeletal proteins. The armadillo repeat is essential for their adapter protein function in cell junctions.

Beta-catenin participates in cell signaling pathways such as the Wnt pathway. When Wnt signals bind to the frizzled receptor, beta-catenin accumulates in the cytoplasm and translocates to the nucleus, where it binds transcription factors to regulate gene expression. Unlike other catenins with tissue-specific variants, vertebrates have only a single highly conserved beta-catenin variant.

P120-catenin stabilizes glutamate receptors on the synaptic membrane, maintaining long-term potentiation essential for memory formation. It prevents neural cadherin endocytosis and promotes cadherin clustering at synaptic junctions. Downregulating p120 disrupts adhesion between pre- and postsynaptic neurons, impairing synaptic communication and plasticity.