期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：2
页码：590-595
DOI：10.1073/pnas.1418515112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMechanical stimuli (pressure, shear stress, membrane stretch, etc.) are a basic form of stimulation that can induce physiological responses in many body organs (skin, muscle, ear, lung, airway, kidney, blood vessels, etc.). The current dogma in sensory systems is that mechanical stimuli are mainly transduced by force-gated ion channels. Our study reveals a previously unidentified cascade for mechanotransduction in neurons and suggests that G protein-coupled receptors may have an overlooked function as mechanical sensors. This finding establishes a molecular mechanism through which the nose sends an afferent signal of breathing to the brain to facilitate integration of orofacial sensation and synchronize delta/theta-band activity in certain brain regions with respiration. 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.
