GIPC3 couples to MYO6 and PDZ domain proteins and shapes the hair cell apical region

GIPC3 has been implicated in auditory function. Initially localized to the cytoplasm of inner and outer hair cells of the cochlea, GIPC3 increasingly concentrated in cuticular plates and at cell junctions over the first two weeks of postnatal development. Early postnatal Gipc3KO/KO mice had mostly normal mechanotransduction currents, but by one month of age they had a complete loss of their auditory brainstem response. During postnatal development, cuticular plates rounded up in Gipc3KO/KO hair cells, then degenerated after postnatal day 15. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. In addition, junctions between inner hair cells and intervening inner phalangeal cells were severely disrupted in Gipc3KO/KO. Immunoaffinity isolation of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks, and the cuticular plate. Several of these immunoprecipitated proteins contained GIPC-family consensus PDZ binding motifs (PBMs), including MYO18A, which binds directly to the PDZ domain of GIPC3. We propose that GIPC3 and MYO6 couple to PBMs of cytoskeletal and cell-junction proteins to shape the cuticular plate. ### Competing Interest Statement The authors have declared no competing interest.