Molecular pathophysiology of phospholipases A2 and their mediators

About

Phospholipids are major constituents of the intracellular and plasma membranes of eukaryotic cells. They are also present in the extracellular environment, for example in lipid particles such as microvesicles and exosomes released under physiological and pathophysiological conditions, lipoproteins, pulmonary surfactant, the skin lipid barrier, dietary lipids, etc. They are also present in the membranes of viruses, bacteria, parasites, and plants. To date, approximately 10,000 molecular species of phospholipids have been identified (www.lipidmaps.org; www.gerli.fr). Phospholipids are insoluble in water and organize into lipid monolayers or bilayers with other lipids and membrane proteins to confer unique biophysical and biochemical properties to cellular organelles and other lipid particles.

These phospholipids are metabolized by various classes of enzymes, including phospholipase A2 (PLA2), which hydrolyzes these phospholipids in all their forms, but in a regulated and specific manner. In humans, approximately 30 genes encode either intracellular or secreted (sPLA2) PLA2, which participate in phospholipid biosynthesis, membrane remodeling, and metabolism. PLA2 thus plays distinct roles in the metabolism and production of lipid mediators with multiple biological functions. Some sPLA2 also bind to receptors such as PLA2R1, a unique, multifunctional protein belonging to the C-type lectin family, found notably in the kidney and various epithelial and immune cells.

The team's objectives are to identify new functions of sPLA2 and PLA2R1 in various physiological and pathophysiological conditions, with the ultimate goal of identifying sPLA2 and its receptor PLA2R1 as therapeutic targets in human diseases. The projects are designed to be translational, spanning from molecular biology to clinical applications.