Phospholipase A2 Antagonists Inhibit Constitutive Retrograde Membrane Traffic to the Endoplasmic Reticulum

Traffic (Impact Factor: 4.35). 05/2000; 1(6):504 - 511. DOI: 10.1034/j.1600-0854.2000.010608.x


Eukaryotic cells contain a variety of cytoplasmic Ca2+-dependent and Ca2+-independent phospholipase A2s (PLA2s; EC However, the physiological roles for many of these ubiquitously-expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca2+-independent PLA2 (iPLA2) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi-to-endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA2 antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans-Golgi network (TGN), Golgi complex, and the ERGIC-53-positive ER-Golgi-intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA2 enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events.

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    • "It is believed to play a highly protective role against the aging the vesiculation of Golgi and other membranes has been already established and their role in the production of second messenger molecules has been demonstrated [9]. Also, the glycerophospholipids containing PUFA are targets of phospholipase A2 (PLA2) [10], while the lysophosphatidylcholines (lyso-PC), product of PLA2 action, are largely related to changes in the membrane shapes [9] [11] and trigger membrane budding and fission [12] [13]. The molecular mechanisms of the above effects still remain unknown and active research is being conducted in order to find out the relationship between the molecular structure and the elastic properties of membranes containing monounsaturated phosphatidylcholine or monounsaturated/polyunsaturated phosphatidylcholines with and without lyso-PC. "
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    ABSTRACT: We report on the effect of lyso- and polyunsaturated fatty acid (PUFA)- containing lipids on the bending elastic properties of lipid membranes. The bending stiffness of monounsaturated phosphatidylcholine (POPC) bilayers with various molar fractions of an omega-3 containing phosphatidylcholine (PDPC) and/or a lysophosphatidylcholine (lyso-PC) was measured by thermal shape fluctuation analysis (TSFA) performed on quasispherical giant unilamellar vesicles (GUV). Strong evidences of their softening effect on lipid bilayers are provided together with data suggesting different degree of influence of the two molecules on the membrane bending elasticity. The effect of lyso-PC on the bending stiffness of POPC membranes was shown to be stronger than the PDPC. We conclude that the PDPC and lyso-PC are most likely controlling the membrane deformations by modulating its elastic properties.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 10/2014; 460. DOI:10.1016/j.colsurfa.2014.03.055 · 2.75 Impact Factor
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    • "u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / b b a m e m properties of lipids play a substantial role in the fission process [7]. A lipid modifying enzyme, cytoplasmic phospholipase A 2 (PLA 2 ), and especially calcium-independent PLA 2 (iPLA 2 ), is implicated in various intracellular membrane trafficking events, such as the formation of membrane tubules from the Golgi complex and endosomes, membrane tubules from the Golgi complex and endosomes, and membrane fusion events in the secretory and endocytic pathways [8]. iPLA 2 generates inverted corn-shaped lysophospholipids that alter membrane curvature and the intrinsic properties of multicomponent membranes and modulate the line tension at the raft boundaries, which is considered to induce vesicle fission. "
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    ABSTRACT: Phospholipase A(2) (PLA(2)) not only plays a role in the membrane vesiculation system but also mediates membrane-raft budding and fission in artificial giant liposomes. This study aimed to demonstrate the same effects in living cells. Differentiated Caco-2 cells were cultured on filter membranes. MDCK cells were challenged with Influenza virus. The MDCK cultures were harvested for virus titration with a plaque assay. Alkaline phosphatase (ALP), a membrane-raft associated glycosylphosphatidylinositol (GPI)-anchored protein, was 70% released by adding 0.2 mmol/l lysophosphatidylcholine, which was abolished by treatment with a membrane-raft disrupter, methyl-beta-cyclodextrin. Activation of calcium-independent PLA(2) (iPLA(2)) by brefeldin A increased the apical release of ALP by approximately 1.5-fold (p<0.01), which was blocked by PLA(2) inhibitor bromoenol lactone (BEL). BEL also reduced Influenza virus production into the media (<10%) in the MDCK culture. These results suggest that cells utilize inverted corn-shaped lysophospholipids generated by PLA(2) to modulate plasma membrane structure and assist the budding of raft-associated plasma membrane particles, which virus utilizes for its budding. Brush borders are enriched with membrane-rafts and undergo rapid turnover; thus, PLA(2) may be involved in the regulatory mechanism in membrane dynamism. Further, iPLA(2) may provide a therapeutic target for viral infections.
    Biochimica et Biophysica Acta 07/2009; 1788(10):2222-8. DOI:10.1016/j.bbamem.2009.07.015 · 4.66 Impact Factor
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