A photocaged orexin-B for spatiotemporally precise control of orexin signaling
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Date
2022-12-15
Publication Type
Journal Article
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Abstract
Orexin neuropeptides carry out important neuromodulatory functions in the brain, yet tools to precisely control the activation of endogenous orexin signaling are lacking. Here, we developed a photocaged orexin-B (photo-OXB) through a C-terminal photocaging strategy. We show that photo-OXB is unable to activate its cognate receptors in the dark but releases functionally active native orexin-B upon uncaging by illumination with UV-visible (UV-vis) light (370-405 nm). We established an all-optical assay combining photo-OXB with a genetically encoded orexin biosensor and used it to characterize the efficiency and spatial profile of photo-OXB uncaging. Finally, we demonstrated that photo-OXB enables optical control over orexin signaling with fine temporal precision both in vitro and ex vivo. Thus, our photocaging strategy and photo-OXB advance the chemical biological toolkit by introducing a method for the optical control of peptide signaling and physiological function.
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published
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Journal / series
Volume
29 (12)
Pages / Article No.
1729 - 1738
Publisher
Cell Press
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Subject
Orexin-B; Neuropeptides; Photocage; G protein-coupled receptor; Genetically encoded sensors; Biosensor