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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lee, S-H; Schneider, C; Higdon, AN; Darley-Usmar, VM; Chung, CY

Published Date

  • July 2011

Published In

Volume / Issue

  • 12 / 7

Start / End Page

  • 878 - 889

PubMed ID

  • 21438970

Pubmed Central ID

  • PMC3115410

Electronic International Standard Serial Number (EISSN)

  • 1600-0854

International Standard Serial Number (ISSN)

  • 1398-9219

Digital Object Identifier (DOI)

  • 10.1111/j.1600-0854.2011.01195.x

Language

  • eng