gammacatenin

Gammacatenin, more commonly known as plakoglobin, is a cytoplasmic protein belonging to the catenin family and is encoded by the JUP gene in humans. It shares structural similarity with beta-catenin and contains armadillo repeats that mediate protein interactions. Plakoglobin participates in both cell adhesion and signaling processes.

In cells, plakoglobin is a core component of desmosomes, where it binds desmosomal cadherins (desmogleins and desmocollins) and associates with desmoplakin and plakophilins to anchor intermediate filaments to the plasma membrane. This positioning supports strong cell–cell adhesion in tissues subjected to mechanical stress, such as the heart and skin. Plakoglobin can also be found at adherens junctions, where it may interact with classical cadherins, linking them to the cytoskeleton. In addition to its structural roles, plakoglobin can translocate to the nucleus and participate in signaling by forming complexes with TCF/LEF transcription factors, akin to beta-catenin, though its transcriptional activation is generally weaker.

Clinical significance is primarily linked to mutations in JUP. Pathogenic variants cause inherited cardiomyopathies, notably arrhythmogenic right ventricular cardiomyopathy (ARVC). In the cardio-cutaneous syndrome known as Naxos disease, JUP mutations underlie concurrent skin and hair abnormalities due to desmosomal defects. Altered plakoglobin expression or localization has also been reported in various cancers and other diseases, reflecting its dual involvement in adhesion and signaling pathways.

Interactions include desmosomal components such as desmocollins, desmogleins, desmoplakin, and plakophilins, as well as beta-catenin and alpha-catenin. In the nucleus, plakoglobin can associate with TCF/LEF transcription factors to influence gene expression.