catenin

Catenins are a family of cytoplasmic proteins that regulate cell-cell adhesion and intracellular signaling. They are central to adherens junctions, where they connect cadherin receptors to the actin cytoskeleton, and they participate in signaling pathways such as Wnt/beta-catenin.

The core members include alpha-, beta-, and gamma-catenin. Alpha-catenins (alpha-E-catenin, alpha-N-catenin, and alpha-T-catenin) bind to the cadherin–catenin complex and connect to actin filaments, helping to maintain tissue architecture and transmit mechanical forces. Beta-catenin has a dual role: as a structural adaptor at adherens junctions linking cadherins to the cytoskeleton, and as a transcriptional co-activator in the nucleus within the Wnt signaling pathway. In the absence of Wnt signaling, beta-catenin is targeted for degradation by a destruction complex that includes APC, Axin, and GSK-3β; upon Wnt activation, beta-catenin accumulates, enters the nucleus, and interacts with TCF/LEF transcription factors to regulate target genes.

Gamma-catenin, also known as plakoglobin (gene JUP), shares homology with beta-catenin and participates in desmosomal junctions as well as cadherin signaling. It can substitute for beta-catenin in some adhesion contexts and can modulate Wnt signaling, contributing to cellular adhesion and transcriptional regulation.

Other catenins include p120-catenin (CTNND1), which binds to the juxtamembrane region of cadherins to stabilize them and regulate cell–cell adhesion and Rho GTPase signaling, and delta-catenin (CTNND2), a brain-enriched protein implicated in neuronal development and synaptic function.

Dysregulation of catenins, particularly beta-catenin, is linked to developmental disorders and cancer. Mutations in CTNNB1 or alterations in Wnt signaling can disrupt adhesion and promote oncogenic transcriptional programs. Delta- and gamma-catenin are implicated in various diseases, including neurodevelopmental disorders and cardiomyopathies.