CG17192 is a\nPhospholipase That Regulates Signaling\nLipids in the <i>Drosophila</i> Gut upon Infection

The chemoproteomics technique, activity-based protein\nprofiling\n(ABPP), has proven to be an invaluable tool in assigning functions\nto enzymes. The serine hydrolase (SH) enzyme superfamily, in particular,\nhas served as an excellent example in displaying the versatility of\nvarious ABPP platforms and has resulted in a comprehensive cataloging\nof the biochemical activities associated within this superfamily.\nBesides SHs, in mammals, several other enzyme classes have been thoroughly\ninvestigated using ABPP platforms. However, the utility of ABPP platforms\nin fly models remains underexplored. Realizing this knowledge gap,\nleveraging complementary ABPP platforms, we reported the full array\nof SH activities during various developmental stages and adult tissues\nin the fruit fly (Drosophila melanogaster). Following up on this study, using ABPP, we mapped SH activities\nin adult fruit flies in an infection model and found that a gut-resident\nlipase CG17192 showed increased activity during infection. To assign\na biological function to this uncharacterized lipase, we performed\nan untargeted lipidomics analysis and found that phosphatidylinositols\nwere significantly elevated when <i>CG17192</i> was depleted\nin the adult fruit fly gut. Next, we overexpressed this lipase in\ninsect cells, and using biochemical assays, we show that CG17192 is\na secreted enzyme that has phospholipase C (PLC) type activity, with\nphosphatidylinositol being a preferred substrate. Finally, we show\nduring infection that heightened CG17192 regulates phosphatidylinositol\nlevels and, by doing so, likely modulates signaling pathways in the\nadult fruit fly gut that might be involved in the resolution of this\npathophysiological condition.