Abstract
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.
Highlights
Auditory and vestibular hair cells (HCs) are polarized epithelial cells with a unique morphology essential for mechanosensation [1]
The polarized distribution of membrane proteins in epithelial cells is essential for cellular function and is accomplished in part through the Adaptor Proteins (APs)-1 complex [44,45]
It was previously thought that disrupting the entire Adaptor Protein 1 (AP-1) complex was lethal and many of the seminal studies on this complex have been done in cell culture
Summary
Auditory and vestibular hair cells (HCs) are polarized epithelial cells with a unique morphology essential for mechanosensation [1]. Hair bundles at the apical end of HCs are comprised of several rows of actin-filled stereocilia and a single primary cilium called the kinocilium. Upon deflection induced by sound or head movements, hair bundles transduce mechanical stimuli into graded receptor potentials. HCs transmit signals to afferent neurons, and in some cases receive signals from efferent neurons [2,3]. How the HC orchestrates apical and basolateral trafficking of membrane proteins for its unique requirements has not been explored
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