刺胞动物机械感觉细胞作为脊椎动物毛细胞的祖先：古老机械转导复合物的分子靶向

文献信息

中文摘要

将机械刺激转化为电信号是许多生理过程的基础，包括听觉和前庭功能。在脊椎动物毛细胞中，机械电转导复合物（METC）——一种多蛋白且依赖Ca2+的声音和运动受体——位于毛束内静纤毛尖端。跨膜通道样蛋白1和2（TMC1和TMC2）作为该复合物中的机械敏感通道发挥作用。为了研究脊椎动物毛细胞的进化起源，我们评估了刺胞动物刺细胞在细胞和分子水平上是否与脊椎动物毛细胞相关。刺细胞的毛束与脊椎动物毛细胞中发现的毛束相似，包括存在细胞外蛋白系链。刺胞动物的TMC5和TMC7定位于毛束，即推测的MET通道活性位点。MET通道可渗透的FM染料摄取实验表明，机械激活的刺细胞通过其静纤毛束而非类动纤毛的刺丝器摄取染料。RNAi介导的TMC5和TMC7敲低显著减少了Clytia和Nematostella中刺细胞的翻出，表明它们在机械转导中的基本作用。相反，类似实验表明TRP通道NompC在此反应中并非必需。总体而言，我们提供了形态学、行为学、药理学、生物信息学和反向遗传学数据，支持刺胞动物刺细胞与脊椎动物毛细胞的共同祖先之间存在进化关系。我们的发现强调了基于TMC通道的机械转导机制的保守性，并为基于静纤毛束偏转的机械信号起源提供了进化见解。

英文摘要

Conversion of mechanical stimuli into electrical signals underlies many physiological processes, including auditory and vestibular functions. In vertebrate hair cells, the mechanoelectrical transduction complex (METC)-a multiprotein and Ca2+-dependent sound and motion receptor-is located at the stereociliary tips within the hair bundle. Transmembrane channel-like 1 and 2 (TMC1 and TMC2) proteins function as the mechanosensitive channels in this complex. To investigate the evolutionary origins of vertebrate hair cells we have evaluated whether cnidarian nematocytes are related to the vertebrate hair cells at the cellular and molecular levels. The hair-bundles of nematocytes resemble those found in vertebrate hair cells, including the presence of extracellular protein tethers. Cnidarian TMC5 and TMC7 localize to the hair bundles, the proposed site of MET channel activity. MET channel permeant FM dye uptake experiments demonstrate that mechanically activated nematocytes incorporate dye through their stereovillar bundle and not through the kinocilium-like cnidocil. RNAi-mediated knockdown of TMC5 and TMC7 significantly reduced nematocyte eversion in Clytia and Nematostella, pointing to their fundamental role in mechanotransduction. In contrast, similar experiments show that the TRP channel NompC is not required in this response. Overall, we present morphological, behavioral, pharmacological, bioinformatic, and reverse genetics data supporting an evolutionary relationship between the common ancestors of cnidarian nematocytes and vertebrate hair cells. Our findings highlight the conservation of mechanotransduction mechanisms based on TMC channels and offer evolutionary insights to the origin of mechanical signaling based on stereovillar bundle deflection.