Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling

The paper describes the development of a new optogenetic tool called LOVPLD to control the production of the signaling lipid phosphatidic acid (PA) in cells with high spatiotemporal precision. PA is involved in many cellular processes but its pleiotropic nature makes its specific functions difficult to study. Previous optogenetic approaches to manipulate PA used light-induced dimerization to recruit enzymes to membranes, but had high background activity. LOVPLD uses a different strategy by inserting a light-sensitive LOV domain into a potent PA-producing enzyme PLD to directly control its catalytic activity with light. In the dark, LOVPLD is inactive but blue light illumination causes a conformational change in the LOV domain that activates the enzyme. LOVPLD showed 50-fold lower background than previous optoPLDs and its expression was well-tolerated unlike constitutively active PLDs. Combining LOVPLD with light-induced dimerization further lowered background. <a href="https://medium.com/@axialxyz/ultralow-background-membrane-editors-for-spatiotemporal-control-of-phosphatidic-acid-metabolism-and-6f3c948f720b">Website</a>