NYU's Janice Cutler Professor of Chemistry Dirk Trauner and his colleagues published a study in Nature Chemical Biology (April 2019) that demonstrates a new way to remotely control native and fully endogenously encoded pain circuitries in vivo with light. Trauner Group graduate students Johannes Morstein (first author) and Alexander Novak worked on the study called, "Optical control of sphingosine-1-phosphate formation and function."
Abstract: Sphingosine-1-phosphate (S1P) plays important roles as a signaling lipid in a variety of physiological and pathophysiological processes. S1P signals via a family of G-protein-coupled receptors (GPCRs) (S1P1–5) and intracellular targets. Here, we report on photoswitchable analogs of S1P and its precursor sphingosine, respectively termed PhotoS1P and PhotoSph. PhotoS1P enables optical control of S1P1–3, shown through electrophysiology and Ca2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P3-dependent pain hypersensitivity in mice. The hypersensitivity induced by PhotoS1P is comparable to that induced by S1P. PhotoS1P is uniquely suited for the study of S1P biology in cultured cells and in vivo because it exhibits prolonged metabolic stability compared to the rapidly metabolized S1P. Using lipid mass spectrometry analysis, we constructed a metabolic map of PhotoS1P and PhotoSph. The formation of these photoswitchable lipids was found to be light dependent, providing a novel approach to optically probe sphingolipid biology.
This research was supported by the National Institutes of Health, the Swiss National Science Foundation, the German Academic Scholarship Foundation (Studienstiftung) the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad and the Howard Hughes Medical Institute.