L-alpha-glycerylphosphorylcholine inhibits the transfer function of phosphatidylinositol transfer protein alpha.
Phosphatidylinositol transfer protein alpha (PITP-alpha) is a bifunctional phospholipid transfer protein that is highly selective for phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho). Polar lipid metabolites, including L-alpha-glycerylphosphorylcholine (GroPCho), 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-alpha activity. GroPCho inhibited the ability of PITP-alpha 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-alpha-mediated phospholipid transfer. Choline, phosphorylcholine (PCho), 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 GroPCho inhibition with the inhibition being greatest for highly anionic membranes. GroPCho was shown to enhance the binding of PITP-alpha to anionic vesicles. In membranes of low surface charge, phosphatidylethanolamine (PtdEtn) was a determinant enabling the GroPCho inhibition. Anionic charge and PtdEtn content appeared to increase the strength of PITP-alpha-membrane interactions. The GroPCho-enhanced PITP-alpha-membrane binding was sufficient to cause inhibition, but not sufficient to account for the extent of inhibition observed. Processes associated with strengthened PITP-alpha-membrane binding in the presence of GroPCho appeared to impair the phospholipid insertion/extraction process.
Komatsu
Hiroaki
H
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Westerman
Jan
J
Snoek
Gerry T
GT
Taraschi
Theodore F
TF
Janes
Nathan
N
D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D005997:Glycerylphosphorylcholine / Q000494:pharmacology* / Q000502:physiology; D008081:Liposomes / Q000737:chemistry; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000494:pharmacology; D049294:Phospholipid Transfer Proteins; D011485:Protein Binding / Q000187:drug effects
D002352:Carrier Proteins; D008081:Liposomes; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010716:Phosphatidylinositols; D049294:Phospholipid Transfer Proteins; D005997:Glycerylphosphorylcholine