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
  • 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.