RT info:eu-repo/semantics/article T1 Phosphatidylinositol 4,5-Bisphosphate Anchors Cytosolic Group IVA Phospholipase A2to Perinuclear Membranes and Decreases Its Calcium Requirement for Translocation in Live Cells A1 Casas Requena, Javier A1 Gijón, Miguel A. A1 Vigo, Ana G. A1 Crespo, Mariano Sánchez A1 Balsinde, Jesús A1 Balboa, María A. AB 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 A2α, cPLA2α). This enzyme is responsible for generating free arachidonic acid from membrane phospholipids. cPLA2α translocates to perinuclear membranes shortly after cell activation, in a process that is governed by the increased availability of intracellular Ca2+. However, cPLA2α also catalyzes membrane phospholipid hydrolysis in response to agonists that do not mobilize intracellular Ca2+. How cPLA2α 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 cPLA2α 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. SN 1059-1524 YR 2006 FD 2006 LK https://uvadoc.uva.es/handle/10324/64290 UL https://uvadoc.uva.es/handle/10324/64290 LA eng NO Molecular biology of the cell 17, 155–162 (2006). DS UVaDOC RD 03-mar-2025