LRP, LDL receptor-related protein

M. Krieger and J. Herz, Structures and functions of multiligand lipoprotein receptors Macrophage scavenger receptors and LDL receptor-related protein (LRP), Annu. Rev. Biochem. 63 (1994) 601-637. 

U. Beiseigel, W. Weber, G. Ihrke, J. Herz and K.K. Stanley, The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein, Nature 341 (1989) 162-164. 

Cholesterol is absorbed from the intestine and transported to the liver by chylomicron remnants, which are taken up by the low-density lipoprotein (LDL)-receptor-related protein (LRP). 

Catabolism of chylomicron remnants may be viewed as the second step in the processing of chylomicrons. After the loss of apo C-II and other C and A apoproteins, LPL no longer acts upon the remnants, and they leave the capillary surface. Chylomicron remnants are rapidly removed by uptake into liver parenchymal cells via receptor-mediated endocytosis. Apo E is important in this uptake process. The chylomicron receptors in liver are distinct from the B-E receptor that mediates uptake of LDL. The hepatic receptor for chylomicrons binds with apo E, but not apo B-48. Another receptor, known as the LDL receptor-related protein (LRP), may also function in chylomicron uptake. Chylomicron remnants are transported into the lysosomal compartment where acid lipases and proteases complete their degradation. In the liver, fatty acids so released are oxidized or are reconverted to triacylglycerol, which is stored or secreted as VLDL. The cholesterol may be used in membrane synthesis, stored as cholesteryl ester, or excreted in the bile unchanged or as bile acids. 

Receptors Frizzled (Fz) with seven transmembrane a helices associated membrane-bound LDL receptor-related protein (Lrp) required for receptor activity Signal transduction Assembly of multiprotein complex at membrane that inhibits the proteasome-mediated proteolysis of cytosolic p-catenin transcription factor, resulting in its accumulation... 

FIGURE 35-1 The miyor pathwi s involved in the metabolism of chylomicrons synthesized by the intestine and VLDL synthesized by the liver. Chylomicrons are converted to chylomicron remnants by the hydrolysis of their triglycerides by LPL. Chylomicron remnants are rapidly cleared from the plasma by the liver. Remnant receptors include die LDL receptor-related protein (LRP), LDL, and perhaps other receptors. FFA released by LPL is used by muscle tissue as an energy source or taken up and stored by adipose tissue. FFA, free fatty acid HL, hepatic lipase IDL, intermediate-density lipoproteins LDL, low-density lipoproteins LPL, lipoprotein lipase VLDL, very-low-density lipoproteins. 

ApoE Liver 34,145 Chylomicron remnants, VLDL, IDL, HDL Ligand for binding of several lipoproteins to the LDL receptor, to the LDL receptor-related protein (LRP) and possibly to a separate apo-E receptor. 

The best-characterized lipoprotein receptor, the LDL receptor, specifically recognizes apoB-100 and apo E. Therefore, this receptor binds VLDL, IDL, and chylomicron remnants in addition to LDL. The binding reaction is characterized by its saturability and occurs with high affinity and a narrow range of specificity. Other receptors, such as the LDL receptor-related proteins (LRP) and the macrophage scavenger receptor (notably types SR-Al and SR-A2, which are located primarily near the endothelial surface of vascular endothelial cells), have broad specificity and bind many other ligands in addition to the blood lipoproteins. 

Chylomicron remnants are taken up by the liver by receptor-mediated endocytosis, and the cholesteryl esters and triacylglycerols are hydrolyzed and metabolized. Uptake is mediated by a receptor specific for apo E (Figure 25-3), and both the LDL (apo B-lOO, E) receptor and the LRP (LDL receptor-related protein)... 

The LDL receptor also binds to apoE and plays a significant role in the hepatic uptake of chylomicrons and VLDL remnants. However, if LDL receptors are unavailable (as, for example, in a mouse strain that lacks the gene for the LDL receptor), VLDL remnants and chylomicrons are still taken up by the liver even though LDL is not. This indicates the presence of a back-up system for receptor-mediated endocytosis of VLDL remnants and chylomicrons. One back-up receptor is lipoprotein receptor-related protein (LRP), which binds to apoE as well as to a number of other ligands. 

LRP LDL-receptor-related protein NAME nitric oxide s mthase inhibitor... 

Fig. 3. Synthesis, secretion, and transport of lipoprotein lipase (LPL) from the adipocyte to the vascular endothelial surface of adipose tissue. Degradative pathways from the Golgi compartment and cell surface are illustrated. ER, endoplasmic reticulum RAP, receptor-associated protein LRP, LDL receptor-related protein.

LDL receptor-related protein/ ff2-macroglobulin receptor (LRP) Apo-E, lipoprotein lipase, hepatic lipase, thrombospondin. Pseudomonas exotoxin A, a2-macroglobulin, receptor-associated protein (RAP), lactofetrin, t-PA, u-PA, t-PA PAl-l, u-PA PAl-l, elastase-al-antitrypsin liver, brain, lung, adrenal, intestine, kidney, placenta, ovary, testis... 

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