2. Academic Validation
  3. Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing

Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing

  • EMBO Mol Med. 2016 Mar 1;8(3):191-207. doi: 10.15252/emmm.201505523.
Annalisa Buniello 1,  Neil J Ingham 2,  Morag A Lewis 2,  Andreea C Huma 3,  Raquel Martinez-Vega 4,  Isabel Varela-Nieto 5,  Gema Vizcay-Barrena 6,  Roland A Fleck 6,  Oliver Houston 7,  Tanaya Bardhan 7,  Stuart L Johnson 7,  Jacqueline K White 3,  Huijun Yuan 8,  Walter Marcotti 7,  Karen P Steel 1
Affiliations

Affiliations

  • 1 Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK [email protected] [email protected].
  • 2 Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • 3 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
  • 4 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Unit 761, Instituto de Salud Carlos III, Madrid, Spain.
  • 5 Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Unit 761, Instituto de Salud Carlos III, Madrid, Spain.
  • 6 Centre for Ultrastructural Imaging, King's College London, London, UK.
  • 7 Department of Biomedical Science, University of Sheffield, Sheffield, UK.
  • 8 Medical Genetics Center, Southwest Hospital Third Military Medical University, Chongqing, China.
PMID: 26881968 DOI: 10.15252/emmm.201505523
Abstract

WBP2 encodes the WW domain-binding protein 2 that acts as a transcriptional coactivator for Estrogen Receptor α (ESR1) and Progesterone Receptor (PGR). We reported that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse, as well as in two deaf children, each carrying two different variants in the WBP2 gene. The earliest abnormality we detect in Wbp2-deficient mice is a primary defect at inner hair cell afferent synapses. This study defines a new gene involved in the molecular pathway linking hearing impairment to hormonal signalling and provides new therapeutic targets.

Keywords

glutamate excitotoxicity; hearing impairment; hormonal signalling; ribbon synapses; transcriptional coactivator.

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