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

Chatterjee, P.; Morgan, C. P.; Krey, J. F.; Benson, C.; Goldsmith, J.; Bateschell, M.; Ricci, A.; Barr-Gillespie, P. G.

doi:10.1101/2023.02.28.530466

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bioRxiv · 10.1101/2023.02.28.530466

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

Chatterjee, P.·Morgan, C. P.·Krey, J. F.·Benson, C.·Goldsmith, J.·Bateschell, M.·Ricci, A.·Barr-Gillespie, P. G.

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Abstract

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 during postnatal development. Early postnatal Gipc3KO/KO mice had mostly normal mechanotransduction currents, but had no auditory brainstem response at one month of age. Cuticular plates of Gipc3KO/KO hair cells did not flatten during development as did those of controls; moreover, hair bundles were squeezed along the cochlear axis in mutant hair cells. Junctions between inner hair cells and adjacent inner phalangeal cells were also severely disrupted in Gipc3KO/KO cochleas. GIPC3 bound directly to MYO6, and the loss of MYO6 led to altered distribution of GIPC3. Immunoaffinity purification of GIPC3 from chicken inner ear extracts identified co-precipitating proteins associated with adherens junctions, intermediate filament networks, and the cuticular plate. Several of 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. Summary statementThe PDZ-domain protein GIPC3 couples the molecular motors MYO6 and MYO18A to actin cytoskeleton structures in hair cells. GIPC3 is necessary for shaping the hair cells cuticular plate and hence the arrangement of the stereocilia in the hair bundle.

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Chatterjee, P., Morgan, C. P., Krey, J. F., Benson, C., Goldsmith, J., Bateschell, M., Ricci, A., Barr-Gillespie, P. G.. 2023-03-01. GIPC3 couples to MYO6 and PDZ domain proteins and shapes the hair cell apical region. https://doi.org/10.1101/2023.02.28.530466

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