Wang Zhongying, Ma Qingping, Lu Jiawen, Cui Xiaochen, Chen Haifeng, Wu Hao, Huang Zhiwu
Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2021 May 11;9:638530. doi: 10.3389/fcell.2021.638530. eCollection 2021.
Among the vertebrate lineages with different hearing frequency ranges, humans lie between the low-frequency hearing (1 kHz) of fish and amphibians and the high-frequency hearing (100 kHz) of bats and dolphins. Little is known about the mechanism underlying such a striking difference in the limits of hearing frequency. Prestin, responsible for cochlear amplification and frequency selectivity in mammals, seems to be the only candidate to date. Mammalian prestin is densely expressed in the lateral plasma membrane of the outer hair cells (OHCs) and functions as a voltage-dependent motor protein. To explore the molecular basis for the contribution of prestin in hearing frequency detection, we collected audiogram data from humans, dogs, gerbils, bats, and dolphins because their average hearing frequency rises in steps. We generated stable cell lines transfected with human, dog, gerbil, bat, and dolphin prestins (hPres, dPres, gPres, bPres, and nPres, respectively). The non-linear capacitance (NLC) of different prestins was measured using a whole-cell patch clamp. We found that the / of bPres and nPres was significantly higher than that of humans. The of hPres was more hyperpolarized than that of nPres. The values of hPres and bPres were higher than that of nPres. We further analyzed the relationship between the high-frequency hearing limit ( ) and the functional parameters ( , , and / ) of NLC among five prestins. Interestingly, no significant correlation was found between the functional parameters and . Additionally, a comparative study showed that the amino acid sequences and tertiary structures of five prestins were quite similar. There might be a common fundamental mechanism driving the function of prestins. These findings call for a reconsideration of the leading role of prestin in hearing frequency perception. Other intriguing kinetics underlying the hearing frequency response of auditory organs might exist.
在具有不同听力频率范围的脊椎动物谱系中,人类介于鱼类和两栖动物的低频听力(1千赫兹)与蝙蝠和海豚的高频听力(100千赫兹)之间。关于听力频率极限存在如此显著差异的潜在机制,我们知之甚少。在哺乳动物中负责耳蜗放大和频率选择性的prestin,似乎是迄今为止唯一的候选因素。哺乳动物的prestin在外毛细胞(OHC)的外侧质膜中密集表达,并作为一种电压依赖性运动蛋白发挥作用。为了探究prestin在听力频率检测中发挥作用的分子基础,我们收集了人类、狗、沙鼠、蝙蝠和海豚的听力图数据,因为它们的平均听力频率呈阶梯式上升。我们构建了分别转染人类、狗、沙鼠、蝙蝠和海豚prestin(分别为hPres、dPres、gPres、bPres和nPres)的稳定细胞系。使用全细胞膜片钳测量不同prestin的非线性电容(NLC)。我们发现bPres和nPres的/显著高于人类。hPres的比nPres的更超极化。hPres和bPres的 值高于nPres。我们进一步分析了五种prestin的高频听力极限()与NLC的功能参数( 、 和/)之间的关系。有趣的是,在功能参数和之间未发现显著相关性。此外,一项比较研究表明,五种prestin的氨基酸序列和三级结构非常相似。可能存在一种驱动prestin功能的共同基本机制。这些发现要求我们重新审视prestin在听力频率感知中的主导作用。听觉器官的听力频率响应可能存在其他有趣的动力学机制。