In Vivo Production And Accumulation of Phosphatidic Acid

Lipids help regulate membrane fusion by recruiting certain proteins to regions of the plasma membrane. Phospholipase D (PLD) is an enzyme that converts the lipid phosphatidylcholine (PC) into phosphatidic acid (PA), which is a lipid that is thought to be critical to the process of exocytosis because it stabilizes the fusion pore. Lipids are beneficial to the membrane fusion process because they can alter the membrane shape. It has been proposed that PA, a negative curvature favoring lipid, stabilizes the location on the membrane where fusion occurs due to the small size of its head group. A negative curvature means the lipids bend so their head groups are closer together. PA has an inverted conical shape which is why it favors a negative curvature. It is known that PA is needed at the membrane fusion site, but what is unknown is the timing of PA production and accumulation. The goal of this research is to map PLD and PA during vesicle docking and fusion. More specifically, this research will study whether PA or PLD accumulates at Syx domains. Syx is a protein that localizes at junctions between cells. It is hypothesized that Syx isolates PA at the membrane fusion site in order to provide membrane curvature changes. This research is important because it will clarify aspects of membrane fusion, a critical process, that are unknown. Learning more about membrane fusion can lead to further research in curing diseases due to error in any step of this process.