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Modulation of Membrane Curvature by Phosphatidic Acid and Lysophosphatidic Acid
Author(s) -
Kooijman Edgar E.,
Chupin Vladimir,
de Kruijff Ben,
Burger Koert N. J.
Publication year - 2003
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2003.00086.x
Subject(s) - phosphatidic acid , lysophosphatidic acid , phosphatidylethanolamine , phospholipase d , lipid bilayer , biochemistry , diacylglycerol kinase , biophysics , chemistry , biology , microbiology and biotechnology , membrane , phosphatidylcholine , phospholipid , signal transduction , protein kinase c , receptor
The local generation of phosphatidic acid plays a key role in the regulation of intracellular membrane transport through mechanisms which are largely unknown. Phosphatidic acid may recruit and activate downstream effectors, or change the biophysical properties of the membrane and directly induce membrane bending and/or destabilization. To evaluate these possibilities, we determined the phase properties of phosphatidic acid and lysophosphatidic acid at physiological conditions of pH and ion concentrations. In single‐lipid systems, unsaturated phosphatidic acid behaved as a cylindrical, bilayer‐preferring lipid at cytosolic conditions (37 °C, pH 7.2, 0.5 m m free Mg 2+ ), but acquired a type‐II shape at typical intra‐Golgi conditions, a mildly acidic pH and submillimolar free Ca 2+ (pH 6.6–5.9, 0.3 m m Ca 2+ ). Lysophosphatidic acid formed type‐I lipid micelles in the absence of divalent cations, but anhydrous cation‐lysophosphatidic acid bilayer complexes in their presence. These data suggest a similar molecular shape for phosphatidic acid and lysophosphatidic acid at cytosolic conditions; however, experiments in mixed‐lipid systems indicate that their shape is not identical. Lysophosphatidic acid stabilized the bilayer phase of unsaturated phosphatidylethanolamine, while the opposite effect was observed in the presence of phosphatidic acid. These results support the hypothesis that a conversion of lysophosphatidic acid into phosphatidic acid by endophilin or BARS (50 kDa brefeldin A ribosylated substrate) may induce negative spontaneous monolayer curvature and regulate endocytic and Golgi membrane fission. Alternative models for the regulation of membrane fission based on the strong dependence of the molecular shape of (lyso)phosphatidic acid on pH and divalent cations are also discussed.