The very large G-protein-coupled receptor VLGR1: a component of the ankle link complex required for the normal development of auditory hair bundles

J Neurosci. 2006 Jun 14;26(24):6543-53. doi: 10.1523/JNEUROSCI.0693-06.2006.

Abstract

Sensory hair bundles in the inner ear are composed of stereocilia that can be interconnected by a variety of different link types, including tip links, horizontal top connectors, shaft connectors, and ankle links. The ankle link antigen is an epitope specifically associated with ankle links and the calycal processes of photoreceptors in chicks. Mass spectrometry and immunoblotting were used to identify this antigen as the avian ortholog of the very large G-protein-coupled receptor VLGR1, the product of the Usher syndrome USH2C (Mass1) locus. Like ankle links, Vlgr1 is expressed transiently around the base of developing hair bundles in mice. Ankle links fail to form in the cochleae of mice carrying a targeted mutation in Vlgr1 (Vlgr1/del7TM), and the bundles become disorganized just after birth. FM1-43 [N-(3-triethylammonium)propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] dye loading and whole-cell recordings indicate mechanotransduction is impaired in cochlear, but not vestibular, hair cells of early postnatal Vlgr1/del7TM mutant mice. Auditory brainstem recordings and distortion product measurements indicate that these mice are severely deaf by the third week of life. Hair cells from the basal half of the cochlea are lost in 2-month-old Vlgr1/del7TM mice, and retinal function is mildly abnormal in aged mutants. Our results indicate that Vlgr1 is required for formation of the ankle link complex and the normal development of cochlear hair bundles.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Age Factors
  • Animals
  • Animals, Newborn
  • Blotting, Western / methods
  • Chickens
  • Cochlea / cytology
  • Cochlea / growth & development
  • Dose-Response Relationship, Radiation
  • Electroretinography / methods
  • Epitopes / immunology*
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Fluorescent Antibody Technique / methods
  • Hair Cells, Auditory / growth & development*
  • Hair Cells, Auditory / metabolism*
  • Hair Cells, Auditory / ultrastructure
  • Immunoprecipitation / methods
  • In Vitro Techniques
  • Mass Spectrometry / methods
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Microscopy, Immunoelectron / methods
  • Patch-Clamp Techniques / methods
  • Pyridinium Compounds / pharmacokinetics
  • Quaternary Ammonium Compounds / pharmacokinetics
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / physiology*
  • Retina / metabolism
  • Retina / ultrastructure

Substances

  • Epitopes
  • FM1 43
  • Mass1 protein, mouse
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Receptors, G-Protein-Coupled