G protein-coupled odorant receptors underlie mechanosensitivity in mammalian olfactory sensory neurons

Abstract

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. , but our understanding of the mechanical sensors is still limited. We previously discovered that some OSNs in the mammalian nose responded to mechanical stimulation (4), a feature that may allow the nose to carry an afferent signal of breathing to the brain and facilitate binding of orofacial sensation (5). In the current study, we aim to identify the mechanical sensor(s) and mechanotransduction pathway in OSNs.In mammals, smell perception depends on a large family of ORs expressed in OSNs. Out of a repertoire of >1,000 ORs (6, 7), each OSN expresses a single type, which determines its response profile and central target in the brain. Binding of odorant molecules with specific ORs activates the olfactory G protein G olf , which in turn activates type III adenylyl cyclase (ACIII). ACIII activation causes increased production of cAMP, which opens a cyclic nucleotide-gated cation (CNG) channel. The inward current via the CNG channel is further amplified by Cl − outflow through a calcium-activated Cl − channel. This transduction cascade leads to depolarization of OSNs, which fire action potentials carrying the odor information to the brain (8). OSNs expressing the same OR are scattered in one of the few broadly defined zones in the olfactory epithelium, but their axons typically converge onto a pair of glomeruli in the olfactory bulb (9).Here we report that disruption of the olfactory signal transduction cascade completely eliminates mechanical responses in OSNs. OSNs expressing different receptor types display differential responses to mechanical stimuli. For instance, I7, M71, and SR1 neurons have much stronger mechanical responses than MOR23 and mOR-EG neurons. Loss-of-function mutation of the I7 receptor, genetic switch of the M71 receptor, or ablation of the SR1 receptor, abolishes or dramatically reduces mechanical responses in the host OSNs. Furthermore, ectopic expression of the I7 receptor restores mechanosensitivity in loss-of-function mutant I7 cells. ...

Spontaneous activity in the piriform cortex extends the dynamic range of cortical odor coding

“…What drives spontaneous spiking in the PC? Mechanosensitive effects of nasal airflow across the olfactory epithelium (30) are not involved, because tracheotomizing mice to bypass the nasal airway did not alter the activity (SL: 1.10 ± 0.06 Hz, mean ± SEM, n = 3 mice, 1,659 cells; SP: 0.77 ± 0.06 Hz, n = 3 mice, 406 cells; not significantly different from corresponding controls, P > 0.1, oneway ANOVA with Tukey's post hoc test) ( Fig. 2A).…”

Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses

“…Although it was well known that forces such as gravity and friction act on organisms and affect their function and structure, it is only in the last two decades that the complex processes by which these forces are sensed by cells is becoming clear (37,48,55,98). Cells and indeed cellular structures respond to external forces in a manner similar to chemical signaling where chemicals (ligands) bind to specific receptors on cells and initiate cellular signaling and an eventual response (24,26,36). Likewise, mechanical signaling or mechanotransduction involves the activation of receptors.…”

Ectopic expression of olfactory receptors and associated G‐protein subunits in the head integument of the amphihaline migratory fish hilsa Tenualosa ilisha

“…This implies the possibility of a novel counter repairing mechanism in migratory fish such as the T. ilisha . Further, in mammals ORs have a direct link to mechanosensitivity in olfactory sensory neurons to sense air flow and can retain such property ectopically (Connelly et al ., ). A similar attribute of OR may also be expected in T. ilisha since its upstream migration is performed against the water current of the river.…”