Despite increasing evidence that lipids play key cellular functions and are involved in an increasing number of human diseases, little information is available on their exact function. This is especially the case for phosphatidic acid (PA) that has been shown to be involved in many normal and pathological cellular functions. PA lies in the middle of three-enzymatic pathways, which makes it an ideal signaling integrator. Based on our latest lipidomic approach, we postulate that intracellular compartments have a specific PA composition, but we still do not understand the respective roles of PA species. We now propose to develop a complete PA toolbox to acutely play with PA levels in subcellular compartments, to follow its membrane dynamics and identify partners with a specific focus on secretory vesicle biogenesis and exocytosis, the two faces of neuro(endocrine) secretion for which PA involvement begins to be firmly established but still largely non-understood.
