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 Frank, Takeshi Harayama, Benjamin M. Williams, Abby L. Parrill, Gabor J. Tigyi, Howard Riezman, Ehud Y. Isacoff, Diana M. Bautista, Dirk Trauner

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)623-631
Number of pages9
JournalNature Chemical Biology
Volume15
Issue number6
DOIs
StatePublished - Jun 1 2019
Externally publishedYes

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Lipids
Hypersensitivity
Physiological Phenomena
sphingosine 1-phosphate
Sphingolipids
Sphingosine
Electrophysiology
G-Protein-Coupled Receptors
Cultured Cells
Mass Spectrometry
Light
Pain

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Morstein, J., Hill, R. Z., Novak, A. J. E., Feng, S., Norman, D. D., Donthamsetti, P. C., ... 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; 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 journalArticle

Morstein, J, Hill, RZ, Novak, AJE, Feng, S, Norman, DD, Donthamsetti, PC, Frank, J, Harayama, T, Williams, BM, Parrill, AL, Tigyi, GJ, Riezman, H, Isacoff, EY, Bautista, DM & Trauner, D 2019, 'Optical control of sphingosine-1-phosphate formation and function', Nature Chemical Biology, vol. 15, no. 6, pp. 623-631. https://doi.org/10.1038/s41589-019-0269-7
Morstein J, Hill RZ, Novak AJE, Feng S, Norman DD, Donthamsetti PC et al. Optical control of sphingosine-1-phosphate formation and function. Nature Chemical Biology. 2019 Jun 1;15(6):623-631. https://doi.org/10.1038/s41589-019-0269-7
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. / 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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