A VE-cadherin–PAR3–α-catenin complex regulates the Golgi localization and activity of cytosolic phospholipase A2α in endothelial cells

Phospholipase A 2 enzymes hydrolyze phospholipids to liberate arachidonic acid for the biosynthesis of prostaglandins and leukotrienes. In the vascular endothelium, group IV phospholipase A 2 α (cPLA 2 α) enzyme activity is regulated by reversible association with the Golgi apparatus. Here we provide evidence for a plasma membrane cell adhesion complex that regulates endothelial cell confluence and simultaneously controls cPLA 2 α localization and enzymatic activity. Confluent endothelial cells display pronounced accumulation of vascular endothelial cadherin (VE-cadherin) at cell–cell junctions, and mechanical wounding of the monolayer stimulates VE-cadherin complex disassembly and cPLA 2 α release from the Golgi apparatus. VE-cadherin depletion inhibits both recruitment of cPLA 2 α to the Golgi and formation of tubules by endothelial cells. Perturbing VE-cadherin and increasing the soluble cPLA 2 α fraction also stimulated arachidonic acid and prostaglandin production. Of importance, reverse genetics shows that α-catenin and δ-catenin, but not β-catenin, regulates cPLA 2 α Golgi localization linked to cell confluence. Furthermore, cPLA 2 α Golgi localization also required partitioning defective protein 3 (PAR3) and annexin A1. Disruption of F-actin internalizes VE-cadherin and releases cPLA 2 α from the adhesion complex and Golgi apparatus. Finally, depletion of either PAR3 or α-catenin promotes cPLA 2 α-dependent endothelial tubule formation. Thus a VE-cadherin–PAR3–α-catenin adhesion complex regulates cPLA 2 α recruitment to the Golgi apparatus, with functional consequences for vascular physiology.