desmocollin

Desmocollins are a subfamily of desmosomal cadherins, calcium-dependent cell adhesion molecules that are integral components of desmosomes, specialized intercellular junctions that provide mechanical strength to tissues under stress. In humans, the desmocollin family comprises three transmembrane proteins: DSC1, DSC2, and DSC3.

Structurally, desmocollins have an extracellular domain with cadherin repeats that mediate calcium-dependent adhesion, a single-pass transmembrane segment, and a cytoplasmic tail that interacts with desmosomal plaque proteins such as plakophilins and desmoplakin, anchoring intermediate filaments to the cell membrane. They can form homophilic and, in some contexts, heterophilic interactions with other desmosomal cadherins like desmogleins, contributing to desmosome assembly and stability.

Expression patterns differ by tissue: DSC1 and DSC3 are enriched in stratified epithelia including the epidermis, while DSC2 is expressed broadly in heart and epithelia. Together with plaque proteins, desmocollins support strong cell–cell adhesion, enabling tissues to resist mechanical forces. Desmosome assembly is dynamic and regulated during development, differentiation, and wound healing.

Clinical relevance: Variants in desmocollin genes have been linked to human disease. Mutations in DSC2 and DSC3 have been associated with inherited cardiomyopathy, notably arrhythmogenic right ventricular cardiomyopathy, and with cutaneous abnormalities in case reports. Altered expression of desmocollins has also been observed in various cancers, reflecting a broader role in tissue architecture and cell signaling. Ongoing research seeks to clarify organism-level functions and pathogenic mechanisms.