Optical Control of Lysophosphatidic Acid Signaling
Creators
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1.
New York University
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2.
California Institute of Technology
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.
Copyright and License
Copyright © 2020 American Chemical Society
Acknowledgement
J.M. thanks the German Academic Scholarship Foundation for a fellowship and New York University for a MacCracken fellowship and a Margaret and Herman Sokol fellowship. D.D.N. and G.J.T. were supported by the NCI grant CA092160. A.S. thanks the Swiss National Science Foundation (SNSF) for a postdoctoral fellowship (P2EZP_181623). J.A.F. was supported by the Vollum Institute Fellowship.
Additional Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.0c02154.
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Synthetic procedure for AzoLPA including NMR and HRMS characterization data; molecular modeling data for LPA3 and LPA5; Ca2+ mobilization data control experiments; and a study of AzoLPA metabolism (PDF)
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Additional details
Identifiers
- ISSN
- 1520-5126
Related works
- Is supplemented by
- Supplemental Material: https://pubs.acs.org/doi/10.1021/jacs.0c02154?goto=supporting-info (URL)
Funding
- National Cancer Institute
- CA092160
- Swiss National Science Foundation
- P2EZP_181623
- German National Academic Foundation
- New York University
Dates
- Available
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2020-05-29Published online