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Vol. 17, Issue 1, 155-162, January 2006

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Phosphatidylinositol 4,5-Bisphosphate Anchors Cytosolic Group IVA Phospholipase A₂ to Perinuclear Membranes and Decreases Its Calcium Requirement for Translocation in Live Cells

Institute of Molecular Biology and Genetics, Spanish Research Council, 47003 Valladolid, Spain

Submitted June 17, 2005; Revised September 18, 2005; Accepted October 4, 2005
Monitoring Editor: John York

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 A₂, cPLA₂). This enzyme is responsible for generating free arachidonic acid from membrane phospholipids. cPLA₂ translocates to perinuclear membranes shortly after cell activation, in a process that is governed by the increased availability of intracellular Ca²⁺. However, cPLA₂ also catalyzes membrane phospholipid hydrolysis in response to agonists that do not mobilize intracellular Ca²⁺. How cPLA₂ 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 cPLA₂ 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.

Abbreviations used: AA, arachidonic acid; [Ca²⁺]_i, intracellular Ca²⁺ concentration; cPLA₂, cytosolic croup IVA phospholipase A₂; PtdIns, phosphatidylinositol.

^* Present address: Department of Pharmacology, University of Colorado Health Sciences Center, Mail Stop 8303, P.O. Box 6511, Aurora, CO 80045.

Address correspondence to: Jesús Balsinde (jbalsinde{at}ibgm.uva.es) or María A. Balboa (mbalboa{at}ibgm.uva.es).

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