Open AccessOptical control of sphingosine-1-phosphate formation and function
Author(s) -
Johannes Morstein,
Rose Z. Hill,
A. Novák,
Suihan Feng,
Dean C. Norman,
Prashant Donthamsetti,
James A. Frank,
Takeshi Harayama,
Benjamin M. Williams,
Abby L. Parrill,
Gábor Tigyi,
Howard Riezman,
Ehud Y. Isacoff,
Diana M. Bautista,
Dirk Trauner
Publication year - 2019
Publication title -
nature chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.412
H-Index - 216
eISSN - 1552-4469
pISSN - 1552-4450
DOI - 10.1038/s41589-019-0269-7
Subject(s) - sphingosine , sphingosine 1 phosphate , g protein coupled receptor , sphingolipid , receptor , lipid signaling , microbiology and biotechnology , intracellular , sphingosine 1 phosphate receptor , in vivo , biology , biochemistry , signal transduction , chemistry , biophysics
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.