title: Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport.
abstract: Plasmalogens are a major sub-class of ethanolamine and choline phospholipids in which the sn-1 position has a long chain fatty alcohol attached through a vinyl ether bond. These phospholipids are proposed to play a role in membrane fusion-mediated events. In this study, we investigated the role of the ethanolamine plasmalogen plasmenylethanolamine (PlsEtn) in intracellular cholesterol transport in Chinese hamster ovary cell mutants NRel-4 and NZel-1, which have single gene defects in PlsEtn biosynthesis. We found that PlsEtn was essential for specific cholesterol transport pathways, those from the cell surface or endocytic compartments to acyl-CoA/cholesterol acyltransferase in the endoplasmic reticulum. The movement of cholesterol from the endoplasmic reticulum or endocytic compartments to the cell surface was normal in PlsEtn-deficient cells. Also, vesicle trafficking was normal in PlsEtn-deficient cells, as measured by fluid phase endocytosis and exocytosis, as was the movement of newly-synthesized proteins to the cell surface. The mutant cholesterol transport phenotype was due to the lack of PlsEtn, since it was corrected when NRel-4 cells were transfected with a cDNA encoding the missing enzyme or supplied with a metabolic intermediate that enters the PlsEtn biosynthetic pathway downstream of the defect. Future work must determine the precise role that plasmalogens have on cholesterol transport to the endoplasmic reticulum.
authors.affiliation: Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Munn
authors.forename: Emily
authors.initials: E
authors.lastname: Arnio
authors.forename: Dailan
authors.initials: D
authors.lastname: Liu
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Zoeller
authors.forename: Laura
authors.initials: L
authors.lastname: Liscum
mesh_terms: D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004951:Esterification; D005089:Exocytosis; D005372:Filipin; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010955:Plasmalogens / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D010955:Plasmalogens; C020791:phosphatidal ethanolamines; D005372:Filipin; D002784:Cholesterol