Polyunsaturated eicosapentaenoic acid displaces proteins from membrane rafts by altering raft lipid composition

Polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5 (n- 3)) inhibit T lymphocyte activation probably by displacing acylated signali ng proteins from membrane lipid rafts. Under physiological conditions, satu rated fatty acyl residues of such proteins partition into the cytoplasmic m embrane lipid leaflet with high affinity for rafts that are enriched in sat urated fatty acyl-containing lipids. However, the biochemical alteration ca using displacement of acylated proteins from rafts in PUFA-treated T cells is still under debate but could principally be attributed to altered protei n acylation or changes in raft lipid composition. We show that treatment of Jurkat T cells with polyunsaturated eicosapentaenoic acid (20:5 (n-3)) res ults in marked enrichment of PUFAs (20:5; 22:5) in lipids from isolated raf ts. Moreover, PUFAs were significantly incorporated into phosphatidylethano lamine that predominantly resides in the cytoplasmic membrane lipid leaflet . Notably, palmitate-labeled Src family kinase Lck and the linker for activ ation of T cells (LAT) were both displaced from lipid rafts indicating that acylation by PUFAs is not required for protein displacement from rafts in PUFA-treated T cells. In conclusion, these data provide strong evidence tha t displacement of acylated proteins from rafts in PUFA-treated T cells is p redominantly due to altered raft lipid composition.