The role of alpha 2M receptor/LRP in chylomicron remnant metabolism.
A strong candidate for the long-searched CR receptor might be the alpha 2MR/LRP. Presently, we are overseeing a whole series of in vitro experiments from different laboratories that show that LRP expresses all the features for being such a receptor protein. LRP is localized on the liver cell surface, as well as on most other animal cells. It recognizes apo E-enriched lipoproteins as beta-VLDL and CR. There is evidence that CR contain LPL and it has been demonstrated that LPL binds with high affinity to LRP. This has been shown in cell binding experiments with subsequent cross-linking and in direct assays on purified receptor protein. HL, which is expressed in liver cells and localized at the liver cell surface, is also able to bind to LRP. Moreover, LRP is found in endosomes and can mediate the uptake of beta-VLDL and CR. Further studies are necessary to evaluate its role in vivo as well as its regulation. The interplay between the different ligands of this large multifunctional receptor protein needs to be clarified. It should be emphasized here that, by describing LPL as a new mediator of CR uptake in the liver and by providing evidence for a direct interaction between LPL and LRP, the role of LRP in the remnant catabolism has become even more likely.
Beisiegel
U
U
Medical Clinic, University Hospital Hamburg, Germany.
Krapp
A
A
Weber
W
W
Olivecrona
G
G
D000595:Amino Acid Sequence; D000818:Animals; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D002417:Cattle; D002914:Chylomicrons / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008969:Molecular Sequence Data; D011509:Proteoglycans / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D000511:alpha-Macroglobulins / Q000378:metabolism
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D002914:Chylomicrons; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011509:Proteoglycans; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D000511:alpha-Macroglobulins; D006493:Heparin; D008049:Lipase; D008071:Lipoprotein Lipase