Phosphatidylinositol 4,5-bisphosphate anchors cytosolic group IVA phospholipase A2 to perinuclear membranes and decreases its calcium requirement for translocation in live cells.
The eicosanoids are centrally involved in the onset and resolution of inflammatory processes. A key enzyme in eicosanoid biosynthesis during inflammation is group IVA phospholipase A2 (also known as cytosolic phospholipase A2alpha, cPLA2alpha). This enzyme is responsible for generating free arachidonic acid from membrane phospholipids. cPLA2alpha translocates to perinuclear membranes shortly after cell activation, in a process that is governed by the increased availability of intracellular Ca2+. However, cPLA2alpha also catalyzes membrane phospholipid hydrolysis in response to agonists that do not mobilize intracellular Ca2+. How cPLA2alpha interacts with membranes under these conditions is a major, still unresolved issue. Here, we report that phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] promotes translocation of cPLA2alpha to perinuclear membranes of intact cells in a manner that is independent of rises in the intracellular Ca2+ concentration. PtdIns(4,5)P2 anchors the enzyme to perinuclear membranes and allows for a proper interaction with its phospholipid substrate to release arachidonic acid.
Casas
Javier
J
Institute of Molecular Biology and Genetics, Spanish Research Council, 47003 Valladolid, Spain.
Gijón
Miguel A
MA
Vigo
Ana G
AG
Crespo
Mariano Sánchez
MS
Balsinde
Jesús
J
Balboa
María A
MA
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D003600:Cytosol / Q000201:enzymology*; D054513:Group IV Phospholipases A2; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000187:drug effects / Q000201:enzymology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D021381:Protein Transport
D019269:Phosphatidylinositol 4,5-Diphosphate; C516390:Pla2g4a protein, mouse; D016718:Arachidonic Acid; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human; D054467:Phospholipases A2; D002118:Calcium