iHuman Institute, ShanghaiTech University, Shanghai, China.
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
Sci Adv. 2019 Apr 17;5(4):eaav7803. doi: 10.1126/sciadv.aav7803. eCollection 2019 Apr.
Inner ear hair cells (HCs) detect sound through the deflection of mechanosensory stereocilia. Stereocilia are inserted into the cuticular plate of HCs by parallel actin rootlets, where they convert sound-induced mechanical vibrations into electrical signals. The molecules that support these rootlets and enable them to withstand constant mechanical stresses underpin our ability to hear. However, the structures of these molecules have remained unknown. We hypothesized that αII- and βII-spectrin subunits fulfill this role, and investigated their structural organization in rodent HCs. Using super-resolution fluorescence imaging, we found that spectrin formed ring-like structures around the base of stereocilia rootlets. These spectrin rings were associated with the hearing ability of mice. Further, HC-specific, βII-spectrin knockout mice displayed profound deafness. Overall, our work has identified and characterized structures of spectrin that play a crucial role in mammalian hearing development.
内耳毛细胞 (HCs) 通过机械敏感的静纤毛的偏转而检测声音。静纤毛通过平行的肌动蛋白根插入 HCs 的基板中，在那里将声音引起的机械振动转化为电信号。支持这些根并使它们能够在持续的机械应力下承受的分子是我们听力的基础。然而，这些分子的结构仍然未知。我们假设 αII-和 βII- spectrin 亚基发挥了这一作用，并研究了它们在啮齿动物 HCs 中的结构组织。使用超分辨率荧光成像，我们发现 spectrin 在静纤毛根的基部周围形成环状结构。这些 spectrin 环与小鼠的听力能力有关。此外，HC 特异性的 βII-spectrin 敲除小鼠表现出严重的耳聋。总的来说，我们的工作已经确定并描述了 spectrin 的结构，这些结构在哺乳动物听力发育中起着至关重要的作用。
