Investigating the Molecular Basis of cPLA2α Membrane Bending

Abstract

Signal transduction mediates disease through key molecular targets that initiate signaling networks. As protein-lipid interactions have been examined in the literature, their role in cellular signaling has become more prevalent as lipid-binding proteins have become high impact drug targets in cancer, inflammation and viral egress. One such target, termed cytosolic phospholipase A2 α (cPLA2α), has been shown to play a key role in the production of the inflammatory mediators prostaglandins and leukotrienes. A novel function of the protein was recently discovered in our lab showing cPLA2α bends zwitterionic membranes using model membranes, a process that is mediated by cPLA2α's ability to deeply penetrate membranes. Others in the field have reported cPLA2α to participate in Fc mediated phagocytosis, intra-Golgi trafficking and endosomal trafficking which further supports cPLA2α's ability to bend membranes in biological processes. In addition, direct evidence has been reported using siRNA showing that cPLA2α induced vesiculation in cells. These results translate into our cellular system as cells transfected with eGFP-cPLA2α form cytoplasmic vesicular structures. We have preliminary evidence showing cPLA2α membrane bending is mediated by oligomerization. The origin of oligomerization is currently under further investigation using both in vitro and cellular techniques.