Role of iPLA(2) in the regulation of Src trafficking and microglia chemotaxis.
Published
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
- 21438970
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