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

Rachel Clemens Grisham, Katie Kindt, Karin Finger-Baier, Bettina Schmid, Teresa Nicolson

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere60866
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 12 2013

Fingerprint

sodium-potassium-exchanging ATPase
pumps
hairs
Adenosine Triphosphatases
Cells
Pumps
mutation
Mutation
mutants
Proteins
proteins
cells
Inner Ear
Membrane Proteins
Lateral Line System
membrane proteins
Membranes
ears
Transcription Factor AP-1
Zebrafish

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

In: PLoS One, Vol. 8, No. 4, e60866, 12.04.2013.

Research output: Contribution to journalArticle

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. In: PLoS One. 2013 ; Vol. 8, No. 4.
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