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キーワード:
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要旨:
The hair cells of the inner ear are polarized epithelial cells with a specialized structure at the apical surface, the
mechanosensitive hair bundle. Mechanotransduction occurs within the hair bundle, whereas synaptic transmission takes
place at the basolateral membrane. The molecular basis of the development and maintenance of the apical and basal
compartments in sensory hair cells is poorly understood. Here we describe auditory/vestibular mutants isolated from
forward genetic screens in zebrafish with lesions in the adaptor protein 1 beta subunit 1 (ap1b1) gene. Ap1b1 is a subunit of
the adaptor complex AP-1, which has been implicated in the targeting of basolateral membrane proteins. In ap1b1 mutants
we observed that although the overall development of the inner ear and lateral-line organ appeared normal, the sensory
epithelium showed progressive signs of degeneration. Mechanically-evoked calcium transients were reduced in mutant hair
cells, indicating that mechanotransduction was also compromised. To gain insight into the cellular and molecular defects in
ap1b1 mutants, we examined the localization of basolateral membrane proteins in hair cells. We observed that the Na+/K+-
ATPase pump (NKA) was less abundant in the basolateral membrane and was mislocalized to apical bundles in ap1b1
mutant hair cells. Accordingly, intracellular Na+ levels were increased in ap1b1 mutant hair cells. Our results suggest that
Ap1b1 is essential for maintaining integrity and ion homeostasis in hair cells.
