29.4:
Catenins
Catenins are a diverse group of adapter proteins that participate in cell-cell adhesion.
Catenins have multiple binding domains that bind cadherins, cytoskeletal components, and various cytoskeletal regulator proteins. Thus, they link the cytoskeleton with cadherins at the cell adhesion sites.
While some catenins, such as plakoglobin and plakophilin, help establish stable connections between cadherins and the intermediate filaments,others, such as alpha- and beta-catenins, dynamically organize the actin cytoskeleton at the plasma membrane.
The organization of actin filaments begins with the binding of beta-catenin to the cytosolic domain of a cadherin molecule. Following this, alpha-catenin binds to the beta-catenin.
Another catenin, p120, also tethers to these complexes and regulates the stability of cadherins on the membrane.
As a few cadherin-catenin complexes cluster together, the alpha-catenins dissociate and form cytosolic dimers.
These alpha-catenin dimers interact strongly with the filamentous actin and help organize actin bundles, thus providing cytoskeletal strength to the cell adhesion sites.
29.4:
Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens junction, the actin cytoskeleton is dynamically organized by the alpha-, beta-, and p120-catenins, both directly or indirectly. For example, α-catenin binds directly to F-actin, whereas p120 regulates actin polymerization via Rho GTPases. At desmosomes, however, the intermediate filaments are organized by the interactions of special catenins called plakoglobin and plakophilin with other proteins such as desmoplakin.
β-catenin and Cell Signaling
In addition to binding cadherins at cell junctions, β-catenin can also function in cell signaling such as the Wnt pathway. In this pathway, the binding of a Wnt signal molecule to the cell surface receptor, termed frizzled, triggers a cascade that increases β-catenin concentration in the cytoplasm. This allows β-catenin to translocate to the nucleus, bind to transcription factors, and regulate the target gene expression. Unlike other catenins that have several tissue-specific variants across organisms, only a single variant of β-catenin is found in vertebrates. This variant is composed of a highly conserved amino acid sequence across all vertebrate species.
p120-catenin and Synaptic Plasticity
The cadherin-catenin complexes are an important part of synaptic plasticity – the strengthening and weakening of synaptic connections involved in memory. For example, p120 is involved in the stabilization of glutamate receptors on the synaptic membrane, thus maintaining long-term potentiation. It is also involved in the stabilization of neural cadherins by preventing their endocytosis and promoting cadherin clustering at synaptic junctions. Downregulating p120 has been shown to prevent adhesion between the pre-and postsynaptic neurons.
Suggested Reading
- Perez-Moreno, Mirna, and Elaine Fuchs. "Catenins: keeping cells from getting their signals crossed." Developmental cell 11.5 (2006): 601-612.
- Moon, Randall T. "Wnt/β-catenin pathway." Science's STKE 2005.271 (2005): cm1-cm1.