Chylomicron remnant metabolism. Role of hepatic lipoprotein receptors in mediating uptake.
Chylomicron remnants are catabolized by the liver, and their uptake within this organ is mediated by the presence of apolipoprotein (apo) E on the surface of these particles. In addition to a receptor for low density lipoproteins (LDL), several lines of evidence suggest that a unique receptor, referred to as the chylomicron remnant or apo E receptor, may be involved in the uptake of these lipoproteins. A possible candidate for the apo E receptor was previously isolated by affinity chromatography and was shown to possess high-affinity binding to apo E-containing lipoproteins, including chylomicron remnants, but not to possess high-affinity binding to apo B-containing LDL. However, it is now known that this fraction contains at least three proteins, all of which bind apo E with high affinity. An Mr congruent to 56,000 fraction contains two proteins that have been identified as the alpha- and beta-subunits of mitochondrial F1-adenosine 5'-triphosphatase (F1-ATPase). Furthermore, purified F1-ATPase binds apo E-containing lipoproteins with high affinity. It is very unlikely that these proteins, presumably isolated from mitochondrial membranes, are involved in chylomicron remnant metabolism. An Mr congruent to 59,000 fraction contains a unique apo E-binding protein that is not an ATPase. This protein appears to be localized to the endoplasmic reticulum of liver cells, but it is unclear whether this protein plays a role in chylomicron remnant catabolism. Furthermore, a cDNA clone coding for a protein that is apparently distinct from the ATPase and the Mr congruent to 59,000 protein has been obtained from a lambda gt11 library.(ABSTRACT TRUNCATED AT 250 WORDS)
Mahley
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RW
Gladstone Foundation Laboratories for Cardiovascular Disease, University of California, San Francisco 94140.
Hui
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DY
Innerarity
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TL
Beisiegel
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U
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D015153:Blotting, Western; D002914:Chylomicrons / Q000378:metabolism*; D004285:Dogs; D004705:Endocytosis; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008970:Molecular Weight; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*
D001057:Apolipoproteins E; D002914:Chylomicrons; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011956:Receptors, Cell Surface; D006180:Proton-Translocating ATPases