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Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells

Academic Article
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Overview

authors

  • Pangrsic, T.
  • Lasarow, L.
  • Reuter, K.
  • Takago, H.
  • Schwander, M.
  • Riedel, D.
  • Frank, T.
  • Tarantino, L. M.
  • Bailey, J. S.
  • Strenzke, N.
  • Brose, N.
  • Mueller, Ulrich
  • Reisinger, E.
  • Moser, T.

publication date

  • July 2010

journal

  • Nature Neuroscience  Journal

abstract

  • Inner hair cell ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles per s) are unknown. We found that an aspartate to glycine substitution in the C(2)F domain of the synaptic vesicle protein otoferlin impaired hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. In vitro estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca(2+) signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones replenished vesicles at lower rates than wild-type ones and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer interstimulus intervals. We conclude that replenishment does not match the release of vesicles at mutant active zones in vivo and a sufficient standing RRP therefore cannot be maintained. We propose that otoferlin is involved in replenishing synaptic vesicles.

subject areas

  • Animals
  • Calcium Signaling
  • Deafness
  • Disease Models, Animal
  • Excitatory Postsynaptic Potentials
  • Hair Cells, Auditory, Inner
  • Hearing
  • Membrane Proteins
  • Mice
  • Mice, Neurologic Mutants
  • Mutation, Missense
  • Synapses
  • Synaptic Vesicles
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Identity

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn.2578

PubMed ID

  • 20562868
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Additional Document Info

start page

  • 869

end page

  • 876

volume

  • 13

issue

  • 7

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