Optical Control of Lysophosphatidic Acid Signaling
Johannes Morstein, Mélanie A. Dacheux, Derek D. Norman, Andrej Shemet, Prashant Donthamsetti, Mevlut Citir, James A. Frank, Carsten Schultz, Ehud Y. Isacoff, Abby L. Parrill, Gábor Tigyi, Dirk Trauner
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.