PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing.
Xudong WuMaryna V IvanchenkoHoor Al JandalMarcelo CicconetArtur A IndzhykulianDavid P CoreyPublished in: Nature communications (2019)
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.
Keyphrases
- electron microscopy
- high frequency
- hearing loss
- amino acid
- single cell
- transcranial magnetic stimulation
- cell therapy
- induced apoptosis
- protein protein
- high resolution
- type diabetes
- emergency department
- oxidative stress
- cell cycle arrest
- signaling pathway
- small molecule
- cell death
- cell proliferation
- optic nerve
- drug induced
- electronic health record
- biofilm formation