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Gene Review

Ldlr  -  low density lipoprotein receptor

Rattus norvegicus

Synonyms: LDL receptor, Low-density lipoprotein receptor
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Disease relevance of Ldlr


Psychiatry related information on Ldlr


High impact information on Ldlr


Chemical compound and disease context of Ldlr


Biological context of Ldlr

  • Nucleotide sequence of the rat low density lipoprotein receptor cDNA [15].
  • Within the 5'-flanking region of the hamster LDL receptor gene are three highly conserved imperfect direct repeat sequences of 16 nucleotides each that in the human gene have been demonstrated to regulate transcription [16].
  • The 18 exons of the hamster gene predict an LDL receptor protein of 854 amino acids that is similar in organization and sequence to those predicted from the cDNAs of rat, rabbit, cow, and human [16].
  • The introns occur at precisely the same positions as those previously determined for the human LDL receptor gene [16].
  • Finally, dietary fish oil increased hepatic cholesteryl ester levels and suppressed hepatic cholesterol synthesis rates, suggesting that the up-regulation of hepatic LDL receptor activity in these animals was not simply a response to diminished cholesterol availability in the liver [17].

Anatomical context of Ldlr

  • Hippocampal neurons express high levels of the LDLR related protein (LRP), whereas hippocampal astrocytes are highly positive for LDLR [18].
  • Association of the low-density lipoprotein receptor with caveolae in hamster and rat liver [19].
  • Dietary fish oil had no effect on the receptor-dependent transport of asialofetuin by the liver, suggesting that the effect of fish oil on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physical properties of hepatic membranes [17].
  • LDL uptake per gram tissue was similar for the liver and the adrenal gland and was approximately 50% LDL receptor-dependent in both tissues [20].
  • In the present study of the crushed rat sciatic nerve, a combination of techniques was used to trace the cellular associations of apoE, apoA-I, and the LDL receptor during nerve repair and to determine the distribution of lipid at each stage [21].

Associations of Ldlr with chemical compounds


Physical interactions of Ldlr


Enzymatic interactions of Ldlr

  • OBJECTIVE: LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor [2].

Regulatory relationships of Ldlr


Other interactions of Ldlr

  • LOX-1, the endothelial oxidized LDL receptor might be involved in the pathogenesis of diabetic atherosclerosis [31].
  • In liver homogenates from both hamsters and rats, the fractions with the highest concentrations of LDL receptor coincided with the location of caveolin-1, a marker of the cholesterol-rich caveolae [19].
  • Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels [10].
  • The cytoplasmic domain of E-cadherin contains two putative basal-lateral sorting motifs, which are homologous to sorting signals in the low density lipoprotein receptor, but an alanine scan across tyrosine residues in these motifs did not affect the fidelity of newly synthesized E-cadherin delivery to the basal-lateral membrane of MDCK cells [32].
  • The clearance via both the PAI-1-dependent and the PAI-1-independent mechanisms was inhibited by the receptor-associated protein, a general inhibitor of clearance mediated by the LDL receptor-related protein [33].

Analytical, diagnostic and therapeutic context of Ldlr


  1. Modified HMG-CoA reductase and LDLr regulation is deeply involved in age-related hypercholesterolemia. Pallottini, V., Martini, C., Cavallini, G., Donati, A., Bergamini, E., Notarnicola, M., Caruso, M.G., Trentalance, A. J. Cell. Biochem. (2006) [Pubmed]
  2. Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model. Hinagata, J., Kakutani, M., Fujii, T., Naruko, T., Inoue, N., Fujita, Y., Mehta, J.L., Ueda, M., Sawamura, T. Cardiovasc. Res. (2006) [Pubmed]
  3. Identification of a cell line that expresses a cell surface and a soluble form of the gp330/receptor-associated protein (RAP) Heymann nephritis antigenic complex. Orlando, R.A., Farquhar, M.G. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. An antibody fragment from a phage display library competes for ligand binding to the low density lipoprotein receptor family and inhibits rhinovirus infection. Hodits, R.A., Nimpf, J., Pfistermueller, D.M., Hiesberger, T., Schneider, W.J., Vaughan, T.J., Johnson, K.S., Haumer, M., Kuechler, E., Winter, G. J. Biol. Chem. (1995) [Pubmed]
  5. Estrogen replacement during hypoalbuminemia may enhance atherosclerotic risk. Joles, J.A., Bijleveld, C., van Tol, A., Geelen, M.J., Koomans, H.A. J. Am. Soc. Nephrol. (1997) [Pubmed]
  6. Serum deprivation increases the expression of low density lipoprotein receptor-related protein in primary cultured rat astrocytes. Jo, I., Im, H.M., Shin, H.J., Won Cho, K., Jung, M., Kim, S.D., Kim Jeong, J., Ahn Jo, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  7. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant. Hunziker, W., Harter, C., Matter, K., Mellman, I. Cell (1991) [Pubmed]
  8. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Poirier, J. Trends Neurosci. (1994) [Pubmed]
  9. Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat. Rudling, M., Parini, P., Angelin, B. J. Clin. Invest. (1997) [Pubmed]
  10. Regulation of rat hepatic low density lipoprotein receptors. In vivo stimulation by growth hormone is not mediated by insulin-like growth factor I. Rudling, M., Olivecrona, H., Eggertsen, G., Angelin, B. J. Clin. Invest. (1996) [Pubmed]
  11. Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo. Rudling, M., Angelin, B. J. Clin. Invest. (1993) [Pubmed]
  12. Effects of gender on hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and LDL receptor in hereditary analbuminemia. Shin, Y., Vaziri, N.D., Willekes, N., Kim, C.H., Joles, J.A. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  13. Amiodarone-induced hypercholesterolemia is associated with a decrease in liver LDL receptor mRNA. Hudig, F., Bakker, O., Wiersinga, W.M. FEBS Lett. (1994) [Pubmed]
  14. Thyroid hormone rapidly induces hepatic LDL receptor mRNA levels in hypophysectomized rats. Ness, G.C., Zhao, Z. Arch. Biochem. Biophys. (1994) [Pubmed]
  15. Nucleotide sequence of the rat low density lipoprotein receptor cDNA. Lee, L.Y., Mohler, W.A., Schafer, B.L., Freudenberger, J.S., Byrne-Connolly, N., Eager, K.B., Mosley, S.T., Leighton, J.K., Thrift, R.N., Davis, R.A. Nucleic Acids Res. (1989) [Pubmed]
  16. Structure of the hamster low density lipoprotein receptor gene. Bishop, R.W. J. Lipid Res. (1992) [Pubmed]
  17. Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat. Ventura, M.A., Woollett, L.A., Spady, D.K. J. Clin. Invest. (1989) [Pubmed]
  18. Implication of apoE isoforms in cholesterol metabolism by primary rat hippocampal neurons and astrocytes. Rapp, A., Gmeiner, B., Hüttinger, M. Biochimie (2006) [Pubmed]
  19. Association of the low-density lipoprotein receptor with caveolae in hamster and rat liver. Ness, G.C., Kohlruss, N., Gertz, K.R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. Use of an anti-low density lipoprotein receptor antibody to quantify the role of the LDL receptor in the removal of chylomicron remnants in the mouse in vivo. Choi, S.Y., Fong, L.G., Kirven, M.J., Cooper, A.D. J. Clin. Invest. (1991) [Pubmed]
  21. A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. Boyles, J.K., Zoellner, C.D., Anderson, L.J., Kosik, L.M., Pitas, R.E., Weisgraber, K.H., Hui, D.Y., Mahley, R.W., Gebicke-Haerter, P.J., Ignatius, M.J. J. Clin. Invest. (1989) [Pubmed]
  22. The low-density lipoprotein receptor is regulated by estrogen and forms a functional complex with the estrogen-regulated protein ezrin in pituitary GH3 somatolactotropes. Smith, P.M., Cowan, A., White, B.A. Endocrinology (2004) [Pubmed]
  23. A rice bran oil diet increases LDL-receptor and HMG-CoA reductase mRNA expressions and insulin sensitivity in rats with streptozotocin/nicotinamide-induced type 2 diabetes. Chen, C.W., Cheng, H.H. J. Nutr. (2006) [Pubmed]
  24. Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid. Lopez, J.M., Bennett, M.K., Sanchez, H.B., Rosenfeld, J.M., Osborne, T.E. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  25. Differences in the mechanisms of uptake and endocytosis of small and large chylomicron remnants by rat liver. Windler, E., Greeve, J., Robenek, H., Rinninger, F., Greten, H., Jäckle, S. Hepatology (1996) [Pubmed]
  26. Phosphoinositide binding by the disabled-1 PTB domain is necessary for membrane localization and Reelin signal transduction. Stolt, P.C., Chen, Y., Liu, P., Bock, H.H., Blacklow, S.C., Herz, J. J. Biol. Chem. (2005) [Pubmed]
  27. Chylomicron remnants: hepatic receptors and metabolism. Havel, R.J. Curr. Opin. Lipidol. (1995) [Pubmed]
  28. Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter. Magaña, M.M., Osborne, T.F. J. Biol. Chem. (1996) [Pubmed]
  29. Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes. Brown, N.F., Salter, A.M., Fears, R., Brindley, D.N. Biochem. J. (1989) [Pubmed]
  30. Activation of IP(3)-protein kinase C-alpha signal transduction pathway precedes the changes of plasma cholesterol, hepatic lipid metabolism and induction of low-density lipoprotein receptor expression in 17-beta-oestradiol-treated rats. Marino, M., Distefano, E., Pallottini, V., Caporali, S., Bruscalupi, G., Trentalance, A. Exp. Physiol. (2001) [Pubmed]
  31. Diabetes enhances lectin-like oxidized LDL receptor-1 (LOX-1) expression in the vascular endothelium: possible role of LOX-1 ligand and AGE. Chen, M., Nagase, M., Fujita, T., Narumiya, S., Masaki, T., Sawamura, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  32. Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells. Chen, Y.T., Stewart, D.B., Nelson, W.J. J. Cell Biol. (1999) [Pubmed]
  33. The role of plasminogen activator inhibitor type 1 in the clearance of tissue-type plasminogen activator by rat hepatoma cells. Camani, C., Bachmann, F., Kruithof, E.K. J. Biol. Chem. (1994) [Pubmed]
  34. Loss of resistance to dietary cholesterol in the rat after hypophysectomy: importance of the presence of growth hormone for hepatic low density lipoprotein-receptor expression. Rudling, M., Angelin, B. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  35. Targeting of biotinylated compounds to its target tissue using a low-density lipoprotein receptor-avidin fusion protein. Lehtolainen, P., Wirth, T., Taskinen, A.K., Lehenkari, P., Leppänen, O., Lappalainen, M., Pulkkanen, K., Marttila, A., Marjomäki, V., Airenne, K.J., Horton, M., Kulomaa, M.S., Ylä-Herttuala, S. Gene Ther. (2003) [Pubmed]
  36. Regulation of cholesterol metabolism in the ethionine-induced premalignant rat liver. Erickson, S.K., Lear, S.R., Barker, M.E., Musliner, T.A. J. Lipid Res. (1990) [Pubmed]
  37. Early induction of LDL receptor gene during rat liver regeneration. Bocchetta, M., Bruscalupi, G., Castellano, F., Trentalance, A., Komaromy, M., Fong, L.G., Cooper, A.D. J. Cell. Physiol. (1993) [Pubmed]
  38. Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression. Liao, W., Rudling, M., Angelin, B. Biochem. J. (1996) [Pubmed]
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