Sox3稳定毛细胞静纤毛肌动蛋白核心，对听力至关重要

文献信息

中文摘要

听力依赖于毛细胞静纤毛内肌动蛋白核心的终生稳定性，然而确保这种稳定性的分子机制在很大程度上仍不清楚。在此，我们在小鼠中鉴定转录因子Sox3为该核心结构的关键调控因子。在缺乏Sox3的情况下，静纤毛核心逐渐解体，导致听力损失和机械转导受损。Sox3缺陷的静纤毛对声创伤也更敏感，并且无法修复结构缺口，而Sox3过表达则赋予对噪声诱导损伤的抵抗力。在机制上，Sox3缺失下调毛细胞中的β-胸腺素基因，其中最显著的是Tmsb10，它是肌动蛋白单体可用性的重要调控因子。耗竭Tmsb10可重现Sox3缺陷毛细胞中观察到的核心退变，从而确立Sox3-Tmsb10轴是控制静纤毛肌动蛋白核心终生保存的新型分子机制。该调控通路也代表了噪声诱导听力损失治疗干预的一个有前景的靶点。

英文摘要

Hearing relies on the lifelong stability of the actin core within hair cell stereocilia, yet the molecular mechanisms ensuring this stability are largely unknown. Here, we identify the transcription factor Sox3 as a key regulator of this core structure in mice. In the absence of Sox3, the stereocilia core progressively disassembles, leading to hearing loss and impaired mechanotransduction. Sox3-deficient stereocilia are also more susceptible to acoustic trauma and fail to repair structural gaps, whereas Sox3 overexpression confers resilience against noise-induced damage. Mechanistically, Sox3 deletion downregulates β-thymosin genes in hair cells, most prominently Tmsb10, an essential regulator of actin monomer availability. Depleting Tmsb10 recapitulates the core degeneration observed in Sox3-deficient hair cells, establishing the Sox3-Tmsb10 axis as a novel molecular mechanism governing the lifelong preservation of the stereocilia actin core. This regulatory pathway also represents a promising target for therapeutic intervention in noise-induced hearing loss.