Abstract:
:Group IVA cytosolic phospholipase A(2)alpha (cPLA(2)alpha) plays a role in the microbicidal machinery of immune cells by translocating to phagosomes to initiate the production of antimicrobial eicosanoids. In this work, we have studied the involvement of the cationic cluster of cPLA(2)alpha (Lys(488)/Lys(541)/Lys(543)/Lys(544)) in the translocation of the enzyme to the phagosomal cup in human macrophages responding to opsonized zymosan. Phagocytosis was accompanied by an increased mobilization of free arachidonic acid, which was strongly inhibited by pyrrophenone. In transfected cells, a catalytically active enhanced green fluorescent protein-cPLA(2)alpha translocated to the phagocytic cup, which was corroborated by frustrated phagocytosis experiments using immunoglobulin G-coated plates. However, a cPLA(2)alpha mutant in the polybasic cluster that cannot bind the anionic phospholipid phosphatidylinositol 4, 5-bisphosphate (PIP(2)) did not translocate to the phagocytic cup. Moreover, an enhanced yellow fluorescent protein (EYFP)-cPLA(2)alpha and an enhanced cyan fluorescent protein-pleckstrin homology (PH) domain of the phospholipase Cdelta1 (PLCdelta(1)) construct that specifically recognizes endogenous PIP(2) in the cells both localized at the same sites on the phagosome. High cellular expression of the PH domain inhibited EYFP-cPLA(2)alpha translocation. On the other hand, group V-secreted phospholipase A(2) and group VIA calcium-independent phospholipase A(2) were also studied, but the results indicated that neither of these translocated to the phagosome. Collectively, these data indicate that the polybasic cluster of cPLA(2)alpha (Lys(488)/Lys(541)/Lys(543)/Lys(544)) regulates the subcellular localization of the enzyme in intact cells under physiologically relevant conditions.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Casas J,Valdearcos M,Pindado J,Balsinde J,Balboa MAdoi
10.1194/jlr.M001461subject
Has Abstractpub_date
2010-02-01 00:00:00pages
388-99issue
2eissn
0022-2275issn
1539-7262pii
jlr.M001461journal_volume
51pub_type
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