Optical Control of Lysophosphatidic Acid Signaling

Johannes Morstein, Mélanie A. Dacheux, Derek D. Norman, Andrej Shemet, Prashant C. Donthamsetti, Mevlut Citir, James A. Frank, Carsten Schultz, Carsten Schultz, Ehud Y. Isacoff, Ehud Y. Isacoff, Abby L. Parrill, Gabor J. Tigyi, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Lysophosphatidic acid (LPA) is a phospholipid that acts as an extracellular signaling molecule and activates the family of lysophosphatidic acid receptors (LPA1-6). These G protein-coupled receptors (GPCRs) are broadly expressed and are particularly important in development as well as in the nervous, cardiovascular, reproductive, gastrointestinal, and pulmonary systems. Here, we report on a photoswitchable analogue of LPA, termed AzoLPA, which contains an azobenzene photoswitch embedded in the acyl chain. AzoLPA enables optical control of LPA receptor activation, shown through its ability to rapidly control LPA-evoked increases in intracellular Ca2+ levels. AzoLPA shows greater activation of LPA receptors in its light-induced cis-form than its dark-adapted (or 460 nm light-induced) trans-form. AzoLPA enabled the optical control of neurite retraction through its activation of the LPA2 receptor.

Original languageEnglish (US)
Pages (from-to)10612-10616
Number of pages5
JournalJournal of the American Chemical Society
Volume142
Issue number24
DOIs
StatePublished - Jun 17 2020

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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  • Cite this

    Morstein, J., Dacheux, M. A., Norman, D. D., Shemet, A., Donthamsetti, P. C., Citir, M., Frank, J. A., Schultz, C., Schultz, C., Isacoff, E. Y., Isacoff, E. Y., Parrill, A. L., Tigyi, G. J., & Trauner, D. (2020). Optical Control of Lysophosphatidic Acid Signaling. Journal of the American Chemical Society, 142(24), 10612-10616. https://doi.org/10.1021/jacs.0c02154