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Originally published In Press as doi:10.1194/jlr.M200363-JLR200 on November 4, 2002

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Journal of Lipid Research, Vol. 44, 182-192, January 2003
Copyright © 2003 by Lipid Research, Inc.

Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport

Natalie J. Munn*, Emily Arnio*, Dailan Liu{dagger}, Raphael A. Zoeller{dagger} and Laura Liscum1,*

* Department of Physiology, Tufts University School of Medicine, Boston, MA 02111
{dagger} Department of Physiology and Structural Biology, Boston University School of Medicine, Boston, MA 02118

1 To whom correspondence should be addressed. e-mail: laura.liscum{at}tufts.edu

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.

Abbreviations: CHO, Chinese hamster ovary; [3H]CL-LDL, LDL that is labeled with [3H]cholesteryl linoleate; DHAP, dihydroxyacetone phosphate; DHAPAT, dihydroxyacetone phosphate acyltransferase; ER, endoplasmic reticulum; HBSS, Hank's balanced salt solution; LPDS, lipoprotein-deficient serum; MTT, 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NCS, newborn calf serum; NPC, Niemann-Pick disease type C; PlsEtn, plasmenyethanolamine

Supplementary key words plasmalogen • plasmenylethanolamine • cholesterol • somatic cell mutant


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