The general function of cadherin-23 contributes to the adhesion and structural integrity of the hair cells in the inner ear, particularly in the formation and maintenance of the hair bundle, which is essential for auditory and vestibular function.
Homodimer beta barrel N-termini Ca2+ cofactor required for proper structure folding. Interacts with other cadherins such as Pcdh-25 for maintenance of actin filamentous structures responsible for mechanotransduction. Present on the apical domain of sensory cells in the inner ear organ of Corti, responsible for the stabilization of inner ear hair filaments for mechanotransduction of sound.
Fig. 1. Topology diagram of cadherin-23 EC1+2.
Primary structure involves beta sheets that formulate a beta barrel, which interacts with another beta- alpha barrel to create a homodimer.
Fig. 2. Detail of wild-type and D101G linker regions, respectively. The latter shows a Cl- ion near Ca2+-binding site 2.
The general function of cadherin-23 is to contribute to the adhesion and structural integrity of the hair cells in the inner ear, specifically in the formation and maintenance of the hair bundle, essential for auditory and vestibular fun
Mutations of cadherin-23 impact the elongation of the N-terminus folds result in distinct and influential impact of Ca2+ binding site structure, bring about a reduction of rigidity and folding strength leading to genetically induced deafness as a phenotype. Protocadherin-23 is the upper domain of the tip link responsible for the mechanotransduction and productivity of the gating spring responsible for auditory and vestibular recognition. Protocadherin is generally localized at the organ of Corti of the ear, predominantly at sets of actin filaments of sensory cells bound to cochlear nerve fibers using mechanotransduction to convert sound to electronic stimuli.
Mutations in the gene that encodes cadherin-23, known as CDH23, are associated with various forms of inherited deafness and balance disorders. These mutations can disrupt the normal function of cadherin-23, leading to structural abnormalities in the hair bundle and impairing the transduction of mechanical stimuli into electrical signals, which are crucial for hearing and balance.
The mutation is a missense mutaion, specifically changing the amino acid at position 101 from aspartate (D) to glycine (G). The mutation is located in the extracellular domain of cadherin-23, specifically in the EC1+2 region. The mutant protein (cadherin-23 with the D101G mutation) exhibits a slightly smaller apparent molecular weight compared to the wild type.
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