Cytosolic phospholipase A2a association with the Golgi apparatus regulates vascular function. (360G-Wellcome-080219_Z_06_Z)

We have discovered that cytosolic phospholipase A2a (cPLA2a) is inactivated byassociation with the Golgi apparatus in confluent monolayers of endothelial cells. This inactive pool of enzyme can be released from the Golgi when the monolayer is wounded. It then can bind to target membranes and lead to prostaglandin synthesis. We want to define the biochemical basis of Golgi association. Our evidence (co-immunoprecipitation, co-localisation, siRNA) points strongly to binding of cPLA2 to annexin A1 and other proteins. We shalldefine peptide sequences responsible for cPLA2 binding to the Golgi apparatus.Such peptides will be tested for their ability to promote release of cPLA2 from the Golgi leading to elevation of prostacyclin levels and thus reduction of blood pressure and clotting.