PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing

Nat Commun. 2019 Aug 23;10(1):3801. doi: 10.1038/s41467-019-11712-w.

Abstract

The bundle of stereocilia on inner ear hair cells responds to subnanometer deflections produced by sound or head movement. Stereocilia are interconnected by a variety of links and also carry an electron-dense surface coat. The coat may contribute to stereocilia adhesion or protect from stereocilia fusion, but its molecular identity remains unknown. From a database of hair-cell-enriched translated proteins, we identify Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1), a large, mostly extracellular protein of 4249 amino acids with a single transmembrane domain. Using serial immunogold scanning electron microscopy, we show that PKHD1L1 is expressed at the tips of stereocilia, especially in the high-frequency regions of the cochlea. PKHD1L1-deficient mice lack the surface coat at the upper but not lower regions of stereocilia, and they develop progressive hearing loss. We conclude that PKHD1L1 is a component of the surface coat and is required for normal hearing in mice.

Publication types

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

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Disease Models, Animal
  • Gene Expression Profiling
  • Hair Cells, Auditory, Inner / metabolism*
  • Hair Cells, Auditory, Inner / ultrastructure
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics*
  • Hearing Loss / pathology
  • Hearing*
  • Humans
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Stereocilia / metabolism*
  • Stereocilia / ultrastructure

Substances

  • Receptors, Cell Surface