Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA, 02115, USA.
Decibel Therapeutics, 1325 Boylston Street, Boston, MA, 02215, USA.
Nat Commun. 2019 Aug 23;10(1):3801. doi: 10.1038/s41467-019-11712-w.
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.
内耳毛细胞的静纤毛束对由声音或头部运动产生的亚纳米级挠度作出反应。静纤毛通过各种连接相互连接，并且还带有电子致密的表面涂层。该涂层可能有助于静纤毛附着或防止静纤毛融合，但它的分子身份仍然未知。从富含毛细胞的翻译蛋白数据库中，我们鉴定出多囊肾病和肝疾病 1 样 1（PKHD1L1），这是一种大型的、主要为细胞外的 4249 个氨基酸的蛋白质，具有单一的跨膜结构域。通过连续免疫金扫描电子显微镜，我们发现 PKHD1L1在静纤毛的尖端表达，特别是在耳蜗的高频区。PKHD1L1 缺陷型小鼠在上部而不是下部的静纤毛区域缺乏表面涂层，并且它们逐渐丧失听力。我们的结论是，PKHD1L1是表面涂层的组成部分，是小鼠正常听力所必需的。
