Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat

Authors

  • Nicola Schug,

    1. University of Tübingen, Institute of Human Genetics, Wilhelmstr. 27, 72074 Tübingen, Germany
    2. University of Tübingen, Tübingen Hearing Research Centre, Molecular Genetics, Tübingen, Germany
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    • *

      Authors contributed equally to this work.

  • Claudia Braig,

    1. University of Tübingen, Tübingen Hearing Research Centre (THRC), Molecular Neurobiology, Elfriede-Aulhorn-Straße 5, D-72076 Tübingen, Germany
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    • *

      Authors contributed equally to this work.

  • Ulrike Zimmermann,

    1. University of Tübingen, Tübingen Hearing Research Centre (THRC), Molecular Neurobiology, Elfriede-Aulhorn-Straße 5, D-72076 Tübingen, Germany
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    • *

      Authors contributed equally to this work.

  • Jutta Engel,

    1. University of Tübingen, Institute of Physiology II and Department of Otolaryngology, Tübingen Hearing Research Centre, Tübingen, Germany
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  • Harald Winter,

    1. University of Tübingen, Tübingen Hearing Research Centre (THRC), Molecular Neurobiology, Elfriede-Aulhorn-Straße 5, D-72076 Tübingen, Germany
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  • Peter Ruth,

    1. University of Tübingen, Institute of Pharmacy, Department of Pharmacology and Toxicology, Auf der Morgenstelle 8, Tübingen, Germany
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  • Nikolaus Blin,

    1. University of Tübingen, Institute of Human Genetics, Wilhelmstr. 27, 72074 Tübingen, Germany
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  • Markus Pfister,

    1. University of Tübingen, Tübingen Hearing Research Centre, Molecular Genetics, Tübingen, Germany
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  • Hubert Kalbacher,

    1. University of Tübingen, Medical and Natural Sciences Research Center, Ob dem Himmelreich 7, Tübingen, Germany
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  • Marlies Knipper

    1. University of Tübingen, Tübingen Hearing Research Centre (THRC), Molecular Neurobiology, Elfriede-Aulhorn-Straße 5, D-72076 Tübingen, Germany
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Professor Marlies Knipper, as above.
E-mail: marlies.knipper@uni-tuebingen.de

Abstract

Mutations of the human otoferlin gene lead to an autosomal recessive nonsyndromic form of prelingual, sensorineural deafness (deafness autosomal recessive 9, DFNB9). Several studies have demonstrated expression of otoferlin in the inner ear and brain, and suggested a role of otoferlin in Ca2+-triggered exocytosis. So far, otoferlin expression profiles were solely based on the detection of mRNA. Here, we analysed the expression of otoferlin protein and mRNA using immunohistochemistry, in situ hybridization and RT-PCR in neonatal and mature Wistar rat tissue. In agreement with previous studies, otoferlin expression was found in the brain and in inner and vestibular hair cells. Otoferlin mRNA and protein was, however, also detected in mature outer hair cells of low-frequency processing cochlear turns and in auditory nerve fibres. In outer, inner and vestibular hair cells, otoferlin was subcellularly localized at a considerable distance from the presumed active release sites. Double-staining with the synaptic ribbon marker, C-terminal binding protein 2 (CtBP2), or the presynaptic Ca2+-channel, Cav1.3, both assumed to mark the sites of vesicle fusion and transmitter release, did not colocalize with otoferlin expression and thus do not necessarily support a selected role of otoferlin in Ca2+-triggered exocytosis. The widespread distribution of otoferlin in neurons, nerve fibres and hair cells, and its subcellular distribution extending beyond the regions of synaptic vesicle fusion, i.e. coenrichment with the cytosolic Golgi matrix protein 130 (GM130) in inner hair cells or the early endosomal autoantigen 1 (EEA1) in outer hair cells support instead the idea of a more ubiquitous role of otoferlin in early/recycling endosome trans-Golgi network dynamics.

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