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Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells

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 de...

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Autores principales: Clemens Grisham, Rachel, Kindt, Katie, Finger-Baier, Karin, Schmid, Bettina, Nicolson, Teresa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625210/
https://www.ncbi.nlm.nih.gov/pubmed/23593334
http://dx.doi.org/10.1371/journal.pone.0060866
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author Clemens Grisham, Rachel
Kindt, Katie
Finger-Baier, Karin
Schmid, Bettina
Nicolson, Teresa
author_facet Clemens Grisham, Rachel
Kindt, Katie
Finger-Baier, Karin
Schmid, Bettina
Nicolson, Teresa
author_sort Clemens Grisham, Rachel
collection PubMed
description 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.
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spelling pubmed-36252102013-04-16 Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells Clemens Grisham, Rachel Kindt, Katie Finger-Baier, Karin Schmid, Bettina Nicolson, Teresa PLoS One Research Article 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. Public Library of Science 2013-04-12 /pmc/articles/PMC3625210/ /pubmed/23593334 http://dx.doi.org/10.1371/journal.pone.0060866 Text en © 2013 Clemens-Grisham et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Clemens Grisham, Rachel
Kindt, Katie
Finger-Baier, Karin
Schmid, Bettina
Nicolson, Teresa
Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title_full Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title_fullStr Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title_full_unstemmed Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title_short Mutations in ap1b1 Cause Mistargeting of the Na(+)/K(+)-ATPase Pump in Sensory Hair Cells
title_sort mutations in ap1b1 cause mistargeting of the na(+)/k(+)-atpase pump in sensory hair cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625210/
https://www.ncbi.nlm.nih.gov/pubmed/23593334
http://dx.doi.org/10.1371/journal.pone.0060866
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