l-α-Glycerylphosphorylcholine inhibits the transfer function of phosphatidylinositol transfer protein α

Abstract Phosphatidylinositol transfer protein α (PITP-α) is a bifunctional phospholipid transfer protein that is highly selective for phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho). Polar lipid metabolites, including l -α-glycerylphosphorylcholine (Gro P Cho), increasingly have been linked to changes in cellular function and to disease. In this study, polar lipid metabolites of PtdIns and PtdCho were tested for their ability to influence PITP-α activity. Gro P Cho inhibited the ability of PITP-α to transfer PtdIns or PtdCho between liposomes. The IC 50 of both processes was dependent on membrane composition. d -myo-inositol 1-phosphate and glycerylphosphorylinositol modestly enhanced PITP-α-mediated phospholipid transfer. Choline, phosphorylcholine ( P Cho), CDP-choline, glyceryl-3-phosphate, myo-inositol and d -myo-inositol 1,4,5-trisphosphate had little effect. Membrane surface charge was a strong determinant of the Gro P Cho inhibition with the inhibition being greatest for highly anionic membranes. Gro P Cho was shown to enhance the binding of PITP-α to anionic vesicles. In membranes of low surface charge, phosphatidylethanolamine (PtdEtn) was a determinant enabling the Gro P Cho inhibition. Anionic charge and PtdEtn content appeared to increase the strength of PITP-α-membrane interactions. The Gro P Cho-enhanced PITP-α-membrane binding was sufficient to cause inhibition, but not sufficient to account for the extent of inhibition observed. Processes associated with strengthened PITP-α-membrane binding in the presence of Gro P Cho appeared to impair the phospholipid insertion/extraction process.