Connelly Timothy, Yu Yiqun, Grosmaitre Xavier, Wang Jue, Santarelli Lindsey C, Savigner Agnes, Qiao Xin, Wang Zhenshan, Storm Daniel R, Ma Minghong
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; CNRS, Université de Bourgogne, 21000 Dijon, France;
Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):590-5. doi: 10.1073/pnas.1418515112. Epub 2014 Dec 30.
Mechanosensitive cells are essential for organisms to sense the external and internal environments, and a variety of molecules have been implicated as mechanical sensors. Here we report that odorant receptors (ORs), a large family of G protein-coupled receptors, underlie the responses to both chemical and mechanical stimuli in mouse olfactory sensory neurons (OSNs). Genetic ablation of key signaling proteins in odor transduction or disruption of OR-G protein coupling eliminates mechanical responses. Curiously, OSNs expressing different OR types display significantly different responses to mechanical stimuli. Genetic swap of putatively mechanosensitive ORs abolishes or reduces mechanical responses of OSNs. Furthermore, ectopic expression of an OR restores mechanosensitivity in loss-of-function OSNs. Lastly, heterologous expression of an OR confers mechanosensitivity to its host cells. These results indicate that certain ORs are both necessary and sufficient to cause mechanical responses, revealing a previously unidentified mechanism for mechanotransduction.
机械敏感细胞对于生物体感知外部和内部环境至关重要,并且多种分子已被认为是机械传感器。在此我们报告,气味受体(ORs),一类大型的G蛋白偶联受体,是小鼠嗅觉感觉神经元(OSNs)对化学和机械刺激作出反应的基础。气味转导中关键信号蛋白的基因敲除或OR - G蛋白偶联的破坏会消除机械反应。奇怪的是,表达不同OR类型的OSNs对机械刺激表现出显著不同的反应。假定的机械敏感ORs的基因交换消除或降低了OSNs的机械反应。此外,一种OR的异位表达恢复了功能丧失的OSNs的机械敏感性。最后,一种OR的异源表达赋予其宿主细胞机械敏感性。这些结果表明,某些ORs对于引起机械反应既是必要的也是充分的,揭示了一种以前未被识别的机械转导机制。