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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cochlea / physiology*
  • Hearing Loss / pathology*
  • Hearing Loss / physiopathology*
  • Hearing*
  • Humans
  • Mice
  • Synapses / physiology*
  • Trans-Activators

Substances

  • Adaptor Proteins, Signal Transducing
  • Trans-Activators
  • WBP2 protein, human