Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice.
Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed.
Orsó
E
E
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Broccardo
C
C
Kaminski
W E
WE
Böttcher
A
A
Liebisch
G
G
Drobnik
W
W
Götz
A
A
Chambenoit
O
O
Diederich
W
W
Langmann
T
T
Spruss
T
T
Luciani
M F
MF
Rothe
G
G
Lackner
K J
KJ
Chimini
G
G
Schmitz
G
G
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000648:ultrastructure; D007421:Intestine, Small / Q000473:pathology; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D013631:Tangier Disease / Q000235:genetics* / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol