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"Nakagawa, Takao"
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Insect olfactory receptors are heteromeric ligand-gated ion channels
2008
Insect odorant receptors
In many organisms, from worms to humans, olfactory cues are detected by large families of seven transmembrane-spanning receptors, which have until now been classified as G protein-coupled receptors. Insects, however, have evolved a surprisingly simple and efficient sense of smell in which the odorant receptors require a second component — the ion-channel-forming chaperone protein Or83b — for correct function. In the first of two related papers, Sato
et al
. show that these heteromeric receptors form ligand-gated cation channels that are not dependent on G protein-coupled second messengers, and speculate that other seven transmembrane-spanning proteins may show similar ion channel activity. Wicher
et al
. show that, in addition to direct channel activation, ligand binding to odorant receptors causes G protein-coupled channel activation. This work has implications for the search for insect odorant receptor inhibitors for possible use in controlling host seeking behaviour of disease carrying insects such as the mosquito.
Olfactory cues are detected by large families of seven transmembrane-spanning receptors, which have until now been classified as G-protein-coupled receptors. In insects, these odorant receptors require a second protein (Or83b) for correct function. These heteromeric receptors form ligand-gated cation channels that are not dependent on G protein-coupled second messengers and it is speculated that seven other transmembrane-spanning proteins may show similar ion channel activity.
In insects, each olfactory sensory neuron expresses between one and three ligand-binding members of the olfactory receptor (OR) gene family, along with the highly conserved and broadly expressed Or83b co-receptor
1
,
2
,
3
,
4
,
5
,
6
,
7
,
8
,
9
. The functional insect OR consists of a heteromeric complex of unknown stoichiometry but comprising at least one variable odorant-binding subunit and one constant Or83b family subunit
10
,
11
,
12
,
13
,
14
,
15
,
16
. Insect ORs lack homology to G-protein-coupled chemosensory receptors in vertebrates
17
and possess a distinct seven-transmembrane topology with the amino terminus located intracellularly
10
,
18
. Here we provide evidence that heteromeric insect ORs comprise a new class of ligand-activated non-selective cation channels. Heterologous cells expressing silkmoth, fruitfly or mosquito heteromeric OR complexes showed extracellular Ca
2+
influx and cation-non-selective ion conductance on stimulation with odorant. Odour-evoked OR currents are independent of known G-protein-coupled second messenger pathways. The fast response kinetics and OR-subunit-dependent K
+
ion selectivity of the insect OR complex support the hypothesis that the complex between OR and Or83b itself confers channel activity. Direct evidence for odorant-gated channels was obtained by outside-out patch-clamp recording of
Xenopus
oocyte and HEK293T cell membranes expressing insect OR complexes. The ligand-gated ion channel formed by an insect OR complex seems to be the basis for a unique strategy that insects have acquired to respond to the olfactory environment.
Journal Article
Context-dependent effects of carbon dioxide on cross-modal integration during mosquito flight
by
Nakagawa, Takao
,
Ohta, Kazumi
,
Kazama, Hokto
in
631/158/856
,
692/699/255
,
Aedes - drug effects
2025
To navigate the environment and search for hosts, mosquitoes utilize multiple sensory cues including carbon dioxide (CO₂), visual, olfactory, and humidity cues. However, how mosquitoes shape their behavior by integrating these cues is poorly understood. Here we monitored the flight maneuvers of
Aedes albopictus
in a virtual reality environment where sensory cues were presented in open- or closed-loop. We found that CO₂ enhances optomotor responses to wide-field motion stimuli provided with various angular speeds and contrasts. Furthermore, CO₂ allowed more accurate tracking of a low contrast, visual object whose position was updated in closed-loop. We also found that olfactory preference is bidirectionally modulated by CO₂ depending on the value of odors: CO₂ enhances attraction to host odors whereas it enhances aversion to a repellent. This olfactory enhancement was further contingent on the humidity level. Together, our results highlight the context-dependent impact of CO₂ on cross-modal integration in mosquitoes.
Journal Article
Insect sex-pheromone signals mediated by specific combinations of olfactory receptors
by
Sakurai, T
,
Nishioka, T
,
Nakagawa, T
in
Acetates
,
Alkadienes - metabolism
,
Alkadienes - pharmacology
2005
We describe two male-specific olfactory receptors (ORs) in the silk moth, Bombyx mori, that are mutually exclusively expressed in a pair of adjacent pheromone-sensitive neurons of male antennae: One is specifically tuned to bombykol, the sex pheromone, and the other to bombykal, its oxidized form. Both pheromone ORs are coexpressed with an OR from the highly conserved insect OR subfamily. This coexpression promotes the functional expression of pheromone receptors and confers ligand-stimulated nonselective cation channel activity. The same effects were also observed for general ORs. Both odorant and pheromone signaling pathways are mediated by means of a common mechanism in insects.
Journal Article
Hydrophobic solution functions as a multifaceted mosquito repellent by enhancing chemical transfer, altering object tracking, and forming aversive memory
2024
Developing a safe and potent repellent of mosquitoes applicable to human skins is an effective measure against the spread of mosquito-borne diseases. Recently, we have identified that hydrophobic solutions such as low viscosity polydimethylsiloxane (L-PDMS) spread on a human skin prevent mosquitoes from staying on and biting it. This is likely due to the ability of L-PDMS in wetting mosquito legs and exerting a capillary force from which the mosquitoes attempt to escape. Here we show three additional functions of L-PDMS that can contribute to repel
Aedes albopictus
, by combining physicochemical analysis and behavioral assays in both an arm cage and a virtual flight arena. First, L-PDMS, when mixed with topical repellents and applied on a human skin, enhances the effect of topical repellents in reducing mosquito bites by efficiently transferring them to mosquito legs upon contact. Second, L-PDMS applied to mosquito tarsi compromises visual object tracking during flight, exerting an influence outlasting the contact. Finally, L-PDMS applied to mosquito tarsi acts as an aversive reinforcer in associative learning, making mosquitoes avoid the conditioned odor. These results uncover a multifaceted potential of L-PDMS in altering a sequence of mosquito behaviors from biting a human skin, visual object tracking following takeoff, to the response to an odor linked with L-PDMS.
Journal Article
Surfactants alter mosquito’s flight and physical condition
2023
Mosquitoes carry lethal pathogens for humans and hundreds of thousands of people are killed by mosquito-borne diseases every year. Therefore, controlling mosquitoes is essential to protect the lives of people around the world. Insecticides are highly effective in controlling mosquitoes and have been used extensively worldwide. However, they have potentially harmful effects on biodiversity and environment, and some mosquitoes are resistant to insecticide ingredients and survive upon their application. Therefore, there is a demand for a method to control mosquitoes without using conventional insecticide ingredients. Here, we used
Aedes albopictus
to test whether solutions with low surface tension, particularly surfactant solutions can alter mosquito behavior by spreading over the hydrophobic cuticle of mosquitoes. We found that solutions with low surface tension indeed attached to mosquitoes flying or resting on the wall, and made them fall. In addition, solutions with yet lower surface tension covered the mosquito surface more quickly and widely, knocking down or killing mosquitoes. These results suggest that surfactants such as sodium dioctyl sulfosuccinate can be used to alter mosquito behavior without relying on conventional insecticides.
Journal Article
Mosquito repellence induced by tarsal contact with hydrophobic liquids
by
Nakagawa, Takao
,
Ozawa, Satoshi
,
Matsui, Yoshiaki
in
631/601/1466
,
639/301/923/1030
,
Aedes - drug effects
2020
Mosquito legs have a unique highly water-repellent surface structure. While being beneficial to mosquitoes, the water-repellence of the tarsi enhances the wettability of hydrophobic substances such as oils. This high wettability induces strong attraction forces on a mosquito’s legs (up to 87% of the mosquito’s weight) towards the oil. We studied the landing behaviour of mosquitoes on oil-coated surfaces and observed that the mosquito contact time was reduced compared to that on hydrophilic-liquid-coated surfaces, suggesting that the oil coating induces an escape response. The observed escape behaviour occurred consistently with several hydrophobic liquids, including silicone oil, which is used globally in personal care products. As the repellent effect is similar to multiple hydrophobic substances, it is likely to be mechanically stimulated owing to the physical properties of the hydrophobic liquids and not due to chemical interactions. On human skin, the contact time was sufficiently short to prevent mosquitoes from starting to blood-feed. The secretion of
Hippopotamus amphibius
, which has physical properties similar to those of low-viscosity silicone oil, also triggered an escape response, suggesting that it acts as a natural mosquito repellent. Our results are beneficial to develop new, safe, and effective mosquito-repellent technologies.
Journal Article
Identification and functional characterization of a sex pheromone receptor in the silkmoth Bombyx mori
2004
Sex pheromones released by female moths are detected with high specificity and sensitivity in the olfactory sensilla of antennae of conspecific males. Bombykol in the silkmoth Bombyx mori was the first sex pheromone to be identified. Here we identify a male-specific G protein-coupled olfactory receptor gene, B. mori olfactory receptor 1 (BmOR-1), that appears to encode a bombykol receptor. The BmOR-1 gene is located on the Z sex chromosome, has an eight-exon/seven-intron structure, and exhibits male-specific expression in the pheromone receptor neurons of male moth antenna during late pupal and adult stages. Bombykol stimulation of Xenopus laevis oocytes expressing BmOR-1 and BmGαq elicited robust dose-dependent inward currents on two-electrode voltage clamp recordings, demonstrating that the binding of bombykol to BmOR-1 leads to the activation of a BmGαq-mediated signaling cascade. Antennae of female moths infected with BmOR-1-recombinant baculovirus showed electrophysiological responses to bombykol but not to bombykal. These results provide evidence that BmOR-1 is a G protein-coupled sex pheromone receptor that recognizes bombykol.
Journal Article
Infrared Absorption and Its Sources of CdZnTe at Cryogenic Temperature
by
Oyabu Shinki
,
Wada Takehiko
,
Ishikawa Daichi
in
Absorptivity
,
Cadmium zinc tellurides
,
Cryogenic temperature
2022
To reveal the causes of infrared absorption in the wavelength region between electronic and lattice absorptions, we measured the temperature dependence of the absorption coefficient of p-type low-resistivity (∼102Ωcm) CdZnTe crystals. We measured the absorption coefficients of CdZnTe crystals in four wavelength bands (λ=6.45, 10.6, 11.6, 15.1μm) over the temperature range of T=8.6-300 K with an originally developed system. The CdZnTe absorption coefficient was measured to be α=0.3-0.5 cm-1 at T=300 K and α=0.4-0.9 cm-1 at T=8.6 K in the investigated wavelength range. With an absorption model based on transitions of free holes and holes trapped at an acceptor level, we conclude that the absorption due to free holes at T=150-300 K and that due to trapped-holes at T<50 K are dominant absorption causes in CdZnTe. We also discuss a method to predict the CdZnTe absorption coefficient at cryogenic temperature based on the room-temperature resistivity.
Journal Article
Shape memory alloys for cryogenic actuators
2025
Actuators are widely used in various mechanical products. However, there have been no actuators that can exhibit high actuation stresses and strains at cryogenic temperatures. Although shape memory alloys (SMAs) are attractive candidates for thermally driven actuators with high actuation stresses and strains, the operation of conventional SMAs is limited to a narrow temperature range near the room temperature. Here, we report the shape memory effect under tensile conditions with a high work output across a wide temperature range of 50–270 K in Cu-Al-Mn-based alloys. In addition, a mechanical heat switch using Cu-Al-Mn was designed for thermal insulation in space infrared telescope, and we demonstrated the operation at around 100 K. These results indicate that Cu-Al-Mn SMAs are potential cryogenic actuators with high actuation stress and strain that would contribute to the development of low temperature technologies in various fields including space astronomy, superconductivity, and liquefied gas industry.
Conventional actuators cannot exhibit high performance at cryogenic temperatures. Shunsuke Sato and colleagues demonstrated that Cu-Al-Mn shape memory alloys can provide high work output from 50 K, showing their potential for use in low-temperature technology fields.
Journal Article
The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease
by
Naoki Mugii
,
Fujiko Someya
,
Takao Nakagawa
in
Carbon monoxide
,
Chronic obstructive pulmonary disease
,
Health risk assessment
2016
The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe) scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002), and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease.
Journal Article