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Nat Chem Biol DOI:10.1038/nchembio.1183

Photochemical activation of TRPA1 channels in neurons and animals.

Publication TypeJournal Article
Year of Publication2013
AuthorsKokel, D, Cheung, CYan J, Mills, R, Coutinho-Budd, J, Huang, L, Setola, V, Sprague, J, Jin, S, Jin, YN, Huang, X-P, Bruni, G, Woolf, CJ, Roth, BL, Hamblin, MR, Zylka, MJ, Milan, DJ, Peterson, RT
JournalNat Chem Biol
Volume9
Issue4
Pages257-63
Date Published2013 Apr
ISSN1552-4469
KeywordsAnimals, Behavior, Animal, Cysteine, Electron Transport, Embryo, Nonmammalian, Humans, Ion Channels, Lasers, Light, Light Signal Transduction, Mice, Motor Activity, Mutation, Oxidation-Reduction, Photochemical Processes, Piperazines, Protein Isoforms, Sensory Receptor Cells, Small Molecule Libraries, Structure-Activity Relationship, Transient Receptor Potential Channels, Zebrafish, Zebrafish Proteins
Abstract

Optogenetics is a powerful research tool because it enables high-resolution optical control of neuronal activity. However, current optogenetic approaches are limited to transgenic systems expressing microbial opsins and other exogenous photoreceptors. Here, we identify optovin, a small molecule that enables repeated photoactivation of motor behaviors in wild-type zebrafish and mice. To our surprise, optovin's behavioral effects are not visually mediated. Rather, photodetection is performed by sensory neurons expressing the cation channel TRPA1. TRPA1 is both necessary and sufficient for the optovin response. Optovin activates human TRPA1 via structure-dependent photochemical reactions with redox-sensitive cysteine residues. In animals with severed spinal cords, optovin treatment enables control of motor activity in the paralyzed extremities by localized illumination. These studies identify a light-based strategy for controlling endogenous TRPA1 receptors in vivo, with potential clinical and research applications in nontransgenic animals, including humans.

URLhttp://dx.doi.org/10.1038/nchembio.1183
DOI10.1038/nchembio.1183
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23396078?dopt=Abstract

Alternate JournalNat. Chem. Biol.
PubMed ID23396078
PubMed Central IDPMC3604056
Grant ListR21 MH085205 / MH / NIMH NIH HHS / United States
F31 NS068038 / NS / NINDS NIH HHS / United States
DA026982 / DA / NIDA NIH HHS / United States
P01 NS072040 / NS / NINDS NIH HHS / United States
R01 NS060725 / NS / NINDS NIH HHS / United States
K01MH091449 / MH / NIMH NIH HHS / United States
F31NS068038 / NS / NINDS NIH HHS / United States
MH085205 / MH / NIMH NIH HHS / United States
HL109004 / HL / NHLBI NIH HHS / United States
K01 MH091449 / MH / NIMH NIH HHS / United States
R01 AI050875 / AI / NIAID NIH HHS / United States
F30 DE023033 / DE / NIDCR NIH HHS / United States
R21 DA026982 / DA / NIDA NIH HHS / United States
R01 HL109004 / HL / NHLBI NIH HHS / United States
R01 MH086867 / MH / NIMH NIH HHS / United States
R01NS067688 / NS / NINDS NIH HHS / United States
MH086867 / MH / NIMH NIH HHS / United States
R01 NS067688 / NS / NINDS NIH HHS / United States
R01NS060725 / NS / NINDS NIH HHS / United States