Rho GTPases mediate the regulation of cochlear outer hair cell motility by acetylcholine.
Rho GTPases mediate the regulation of cochlear outer hair cell motility by acetylcholine.
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Rho GTPases 通过乙酰胆碱介导耳蜗外毛细胞运动的调节。
DOI：
10.1074/jbc.m004917200
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
G. Kalinec
中科院分区：
文献类型：
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作者：
Federico Kalinec;Ming Zhang;Raul Urrutia;G. Kalinec
外毛细胞是耳蜗放大器的机械效应器，耳蜗放大器是一个提高哺乳动物耳朵的灵敏度和频率辨别能力的主动过程。在体内，耳蜗放大器的增益由传出神经递质乙酰胆碱通过调节外毛细胞运动来调节。然而，关于乙酰胆碱激活的分子机制知之甚少。在这项研究中，涉及小 GTPases RhoA、Rac1 和 Cdc42 的细胞内信号通路已被确定为外毛细胞运动的调节因子。在以全细胞模式贴片钳的分离的外毛细胞中测量细胞长度（慢速运动）和电诱导运动（快速运动）幅度的变化，通过贴片吸管内部灌注这些小 GTP 酶的不同抑制剂和激活剂，同时用乙酰胆碱进行外部刺激。我们发现乙酰胆碱通过 Rac1 和 Cdc42 激活诱导外毛细胞缩短并同时增加快速运动的幅度。相反，RhoA 和 Rac1 介导的信号通路会诱导外毛细胞伸长并降低快速运动幅度。这两个相反的过程为外毛细胞运动的调节机制提供了基础。
Outer hair cells are the mechanical effectors of the cochlear amplifier, an active process that improves the sensitivity and frequency discrimination of the mammalian ear. In vivo, the gain of the cochlear amplifier is regulated by the efferent neurotransmitter acetylcholine through the modulation of outer hair cell motility. Little is known, however, regarding the molecular mechanisms activated by acetylcholine. In this study, intracellular signaling pathways involving the small GTPases RhoA, Rac1, and Cdc42 have been identified as regulators of outer hair cell motility. Changes in cell length (slow motility) and in the amplitude of electrically induced movement (fast motility) were measured in isolated outer hair cells patch clamped in whole-cell mode, internally perfused through the patch pipette with different inhibitors and activators of these small GTPases while being externally stimulated with acetylcholine. We found that acetylcholine induces outer hair cell shortening and a simultaneous increase in the amplitude of fast motility through Rac1 and Cdc42 activation. In contrast, a RhoA- and Rac1-mediated signaling pathway induces outer hair cell elongation and decreases fast motility amplitude. These two opposing processes provide the basis for a regulatory mechanism of outer hair cell motility.