title: Role of iPLA(2) in the regulation of Src trafficking and microglia chemotaxis.
abstract: Microglia are immune effector cells in the central nervous system (CNS) and their activation, migration and proliferation play crucial roles in brain injuries and diseases. We examined the role of intracellular Ca(2+) -independent phospholipase A(2) (iPLA(2)) in the regulation of microglia chemotaxis toward ADP. Inhibition of iPLA(2) by 4-bromoenol lactone (BEL) or iPLA(2) knockdown exerted a significant inhibition on phosphatidylinositol-3-kinase (PI3K) activation and chemotaxis. Further examination revealed that iPLA(2) knockdown abrogated Src activation, which is required for PI3K activation and chemotaxis. Colocalization studies showed that cSrc-GFP was retained in the endosomal recycling compartment (ERC) in iPLA(2) knockdown cells, but the addition of arachidonic acid (AA) could restore cSrc trafficking to the plasma membrane by allowing the formation/release of recycling endosomes associated with cSrc-GFP. Using BODIPY-AA, we showed that AA is selectively enriched in recycling endosomes. These results suggest that AA is required for the cSrc trafficking to the plasma membrane by controlling the formation/release of recycling endosomes from the ERC.
authors: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
authors: Sang-Hyun
authors: SH
authors: Lee
authors: Claus
authors: C
authors: Schneider
authors: Ashlee N
authors: AN
authors: Higdon
authors: Victor M
authors: VM
authors: Darley-Usmar
authors: Chang Y
authors: CY
authors: Chung
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D001692:Biological Transport; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D022081:Cell Surface Extensions / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054512:Phospholipases A2, Calcium-Independent / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000244:Adenosine Diphosphate; D016718:Arachidonic Acid; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054512:Phospholipases A2, Calcium-Independent; D011993:Recombinant Fusion Proteins; D019061:src-Family Kinases; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene