Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence
| Autor: | Dae-Won Seo, Myunghwan Choi, KyeongJin Kang, Xianlan Wen, Eun Jo Du, Hyung-Wook Kim, Hana Cho, Jae Young Kwon, Tae Jung Ahn, Duk L. Na |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene isoform QH301-705.5 Science Radical free radicals nucleophiles TRPA1 Ion Channels General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Transient receptor potential channel chemistry.chemical_compound 0302 clinical medicine Nucleophile Animals Drosophila Proteins photobiology Biology (General) Receptor Hydrogen peroxide TRPA1 Cation Channel TRPC Cation Channels feeding deterrence photochemistry D. melanogaster General Immunology and Microbiology Chemistry Ecology General Neuroscience chemical nociception food and beverages Feeding Behavior General Medicine 030104 developmental biology Photobiology Electrophile Sunlight Biophysics Medicine Drosophila psychological phenomena and processes 030217 neurology & neurosurgery Neuroscience Research Article |
| Zdroj: | eLife, Vol 5 (2016) eLife |
| ISSN: | 2050-084X |
| Popis: | Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.18425.001 eLife digest Atoms are made up of a nucleus that contains protons and neutrons, which is orbited by electrons. The electrons orbit within shells that surround the nucleus and each shell can contain a specific number of electrons. A particle with an outer shell that is missing one or more electrons will be unstable and highly reactive. It will attempt to achieve a full outer shell either by sharing electrons with another particle, or by donating or stealing an electron. Particles that steal electrons are said to be “electrophilic” (electron-loving) while those that donate them are “nucleophilic”. Electrophilic and nucleophilic particles can damage DNA and proteins. In species from fruit flies to humans, electrophilic substances such as formaldehyde activate a type of ion channel called TRPA1. These ion channels contribute to pain signaling, and their activation triggers unpleasant and painful sensations that deter animals from getting too close to electrophilic substances. However, it is not known if animals have an equivalent mechanism to help them avoid toxic nucleophilic compounds, like carbon monoxide and cyanide. Du, Ahn, Wen, Seo, Na et al. now show that fruit fly neurons produce two versions of the TRPA1 channel: one that is sensitive to electrophiles, plus a second that is sensitive to nucleophiles in addition to electrophiles. The existence of nucleophile-sensitive TRPA1 helps explain why fruit flies avoid feeding in strong sunlight. Ultraviolet radiation in sunlight triggers the production of reactive forms of oxygen that behave as strong nucleophiles. These reactive oxygen species – which can damage DNA – activate the nucleophile-sensitive TRPA1 and thereby trigger the fly’s avoidance behavior. Human TRPA1 responds only to electrophiles and not to nucleophiles. By targeting the nucleophile-sensitive version of insect TRPA1, it may thus be possible to develop insect repellants that humans do not find aversive. Furthermore, TRPA1s from some insect species are more sensitive to nucleophiles than others, with a mosquitoes’ being more sensitive than the fruit flies’. This means that insect repellants that target nucleophile-sensitive TRPA1 could potentially repel malaria-transmitting mosquitoes without affecting other insect species. DOI: http://dx.doi.org/10.7554/eLife.18425.002 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|