Optical control of sphingosine-1-phosphate formation and function

Johannes Morstein; Rose Z. Hill; Alexander J.E. Novak; Suihan Feng; Derek D. Norman; Prashant C. Donthamsetti; James A. Frank; Takeshi Harayama; Benjamin M. Williams; Abby L. Parrill; Gabor J. Tigyi; Howard Riezman; Ehud Y. Isacoff; Diana M. Bautista; Dirk Trauner

doi:10.1038/s41589-019-0269-7

Optical control of sphingosine-1-phosphate formation and function

Johannes Morstein, Rose Z. Hill, Alexander J.E. Novak, Suihan Feng, Derek D. Norman, Prashant C. Donthamsetti, James A. Frank, Takeshi Harayama, Benjamin M. Williams, Abby L. Parrill, Gabor J. Tigyi, Howard Riezman, Ehud Y. Isacoff, Diana M. Bautista, Dirk Trauner

Vollum Institute

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	623-631
Number of pages	9
Journal	Nature Chemical Biology
Volume	15
Issue number	6
DOIs	https://doi.org/10.1038/s41589-019-0269-7
State	Published - Jun 1 2019

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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Morstein, J., Hill, R. Z., Novak, A. J. E., Feng, S., Norman, D. D., Donthamsetti, P. C., Frank, J. A., Harayama, T., Williams, B. M., Parrill, A. L., Tigyi, G. J., Riezman, H., Isacoff, E. Y., Bautista, D. M., & Trauner, D. (2019). Optical control of sphingosine-1-phosphate formation and function. Nature Chemical Biology, 15(6), 623-631. https://doi.org/10.1038/s41589-019-0269-7

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 A.; 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 › peer-review

Morstein, Johannes ; Hill, Rose Z. ; Novak, Alexander J.E. ; Feng, Suihan ; Norman, Derek D. ; Donthamsetti, Prashant C. ; Frank, James A. ; Harayama, Takeshi ; Williams, Benjamin M. ; Parrill, Abby L. ; Tigyi, Gabor J. ; Riezman, Howard ; Isacoff, Ehud Y. ; Bautista, Diana M. ; Trauner, Dirk. / Optical control of sphingosine-1-phosphate formation and function. In: Nature Chemical Biology. 2019 ; Vol. 15, No. 6. pp. 623-631.

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title = "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.",

author = "Johannes Morstein and Hill, {Rose Z.} and Novak, {Alexander J.E.} and Suihan Feng and Norman, {Derek D.} and Donthamsetti, {Prashant C.} and Frank, {James A.} and Takeshi Harayama and Williams, {Benjamin M.} and Parrill, {Abby L.} and Tigyi, {Gabor J.} and Howard Riezman and Isacoff, {Ehud Y.} and Bautista, {Diana M.} and Dirk Trauner",

note = "Funding Information: J.M. thanks the German Academic Scholarship Foundation (Studienstiftung) for a PhD Fellowship. J.M. and A.J.E.N. thank New York University for MacCracken PhD fellowships. T.H. was supported by the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad. D.D.N. and G.Y.T. were supported by NCI grant No. CA092160. H.R. was supported by Sinergia, the Swiss National Science Foundation (No. CRSII3-154405) and the NCCR Chemical Biology funded by the Swiss National Science Foundation (No. 51NF40-160589). D.M.B was supported by NIH grants Nos. AR059385 and NS077224, and by an HHMI Faculty Scholar Award. E.Y.I. was supported by NIH grant 1U01MH109069-01. We thank B. Hetzler for critical discussion of the photophysical characterization and C. Lin for assistance with NMR experiments. S. Lee is acknowledged for performing TNA-α assays with PhotoS1P on S1P receptor subtypes (data not included).",

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AU - Norman, Derek D.

AU - Donthamsetti, Prashant C.

AU - Frank, James A.

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.

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N1 - Funding Information: J.M. thanks the German Academic Scholarship Foundation (Studienstiftung) for a PhD Fellowship. J.M. and A.J.E.N. thank New York University for MacCracken PhD fellowships. T.H. was supported by the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad. D.D.N. and G.Y.T. were supported by NCI grant No. CA092160. H.R. was supported by Sinergia, the Swiss National Science Foundation (No. CRSII3-154405) and the NCCR Chemical Biology funded by the Swiss National Science Foundation (No. 51NF40-160589). D.M.B was supported by NIH grants Nos. AR059385 and NS077224, and by an HHMI Faculty Scholar Award. E.Y.I. was supported by NIH grant 1U01MH109069-01. We thank B. Hetzler for critical discussion of the photophysical characterization and C. Lin for assistance with NMR experiments. S. Lee is acknowledged for performing TNA-α assays with PhotoS1P on S1P receptor subtypes (data not included).

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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) (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.

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