Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport.
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.
Munn
Natalie J
NJ
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Arnio
Emily
E
Liu
Dailan
D
Zoeller
Raphael A
RA
Liscum
Laura
L
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*
D010955:Plasmalogens; C020791:phosphatidal ethanolamines; D005372:Filipin; D002784:Cholesterol