CDH23

CDH23, or cadherin-23, is a protein encoded by the CDH23 gene in humans. It is a member of the cadherin superfamily, a group of calcium-dependent cell adhesion proteins, and is prominently expressed in sensory epithelia such as the inner ear and retina. The protein features a long extracellular region enriched with cadherin repeats, a single transmembrane segment, and a cytoplasmic tail that mediates intracellular interactions.

Structure and function: The extracellular domain of cadherin-23 contains many cadherin repeats that mediate calcium-dependent adhesion between cells. In the inner ear, cadherin-23 participates in forming the tip link between adjacent stereocilia on hair cells, a filament that transmits mechanical forces to mechanotransduction channels and enables hearing. Cadherin-23 operates in concert with protocadherin-15 to form the functional tip link. In the retina, CDH23 is expressed in photoreceptors and other retinal cells; its exact role is less clearly defined but it is believed to contribute to cell adhesion and synaptic organization in retinal tissue.

Genetic clinical relevance: Pathogenic variants in CDH23 cause Usher syndrome type 1F, a recessive disorder characterized by congenital hearing loss, balance problems, and progressive retinitis pigmentosa leading to vision loss. CDH23 mutations can also cause nonsyndromic autosomal recessive deafness (DFNB12) without accompanying vision symptoms. The disease mechanism typically involves disruption of the tip-link adhesion complex and related Usher protein networks, impairing mechanosensory and retinal functions.

Interactions and pathways: The cytoplasmic tail of cadherin-23 binds to scaffolding proteins such as harmonin (USH1C) through PDZ-domain interactions, linking the adhesive complex to the actin cytoskeleton. Interactions with protocadherin-15 and other Usher proteins are central to the assembly and maintenance of the hair-cell apparatus and its signaling capabilities.

Research and applications: Genetic testing identifies CDH23 variants in affected individuals. Mouse and other model organisms are used to study function, disease mechanisms, and potential therapies, including approaches aimed at preserving hair-cell integrity and addressing retinal degeneration.