Role of iPLA(2) in the regulation of Src trafficking and microglia chemotaxis.

Lee SH, Schneider C, Higdon AN, Darley-Usmar VM, Chung CY
Traffic. 2011 12 (7): 878-89

PMID: 21438970 · PMCID: PMC3115410 · DOI:10.1111/j.1600-0854.2011.01195.x

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.

© 2011 John Wiley & Sons A/S.

MeSH Terms (20)

Adenosine Diphosphate Animals Arachidonic Acid Biological Transport Boron Compounds Cell Line Cell Membrane Cell Surface Extensions Chemotaxis Endosomes Enzyme Activation Enzyme Inhibitors Fluorescent Dyes Focal Adhesions Microglia Phosphatidylinositol 3-Kinases Phosphoinositide-3 Kinase Inhibitors Phospholipases A2, Calcium-Independent Recombinant Fusion Proteins src-Family Kinases

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