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) (S1P 1–5 ) 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 S1P 1–3 , shown through electrophysiology and Ca 2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P 3 -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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 623-631 |
| Number of pages | 9 |
| Journal | Nature Chemical Biology |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2019 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Optical control of sphingosine-1-phosphate formation and function. / Morstein, Johannes; Hill, Rose Z.; Novak, Alexander J.E.; Feng, Suihan; Norman, Derek D.; Donthamsetti, Prashant C.; Frank, James; Harayama, Takeshi; Williams, Benjamin M.; Parrill, Abby L.; Tigyi, Gabor J.; Riezman, Howard; Isacoff, Ehud Y.; Bautista, Diana M.; Trauner, Dirk.
In: Nature Chemical Biology, Vol. 15, No. 6, 01.06.2019, p. 623-631.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Optical control of sphingosine-1-phosphate formation and function
AU - Morstein, Johannes
AU - Hill, Rose Z.
AU - Novak, Alexander J.E.
AU - Feng, Suihan
AU - Norman, Derek D.
AU - Donthamsetti, Prashant C.
AU - Frank, James
AU - Harayama, Takeshi
AU - Williams, Benjamin M.
AU - Parrill, Abby L.
AU - Tigyi, Gabor J.
AU - Riezman, Howard
AU - Isacoff, Ehud Y.
AU - Bautista, Diana M.
AU - Trauner, Dirk
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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) (S1P 1–5 ) 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 S1P 1–3 , shown through electrophysiology and Ca 2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P 3 -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.
AB - 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) (S1P 1–5 ) 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 S1P 1–3 , shown through electrophysiology and Ca 2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P 3 -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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85065156504&partnerID=8YFLogxK
U2 - 10.1038/s41589-019-0269-7
DO - 10.1038/s41589-019-0269-7
M3 - Article
VL - 15
SP - 623
EP - 631
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 6
ER -