Journal article
Optical control of sphingosine-1-phosphate formation and function.
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Morstein J
Department of Chemistry, New York University, New York, New York, NY, USA.
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Hill RZ
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
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Novak AJE
Department of Chemistry, New York University, New York, New York, NY, USA.
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Feng S
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
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Norman DD
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
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Donthamsetti PC
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
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Frank JA
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Munich, Germany.
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Harayama T
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
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Williams BM
Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Munich, Germany.
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Parrill AL
Department of Chemistry, University of Memphis, Memphis, TN, USA.
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Tigyi GJ
Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
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Riezman H
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
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Isacoff EY
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
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Bautista DM
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
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Trauner D
Department of Chemistry, New York University, New York, New York, NY, USA. dirktrauner@nyu.edu.
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Published in:
- Nature chemical biology. - 2019
English
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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Language
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Open access status
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green
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/103814
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