lipoprotein receptors


Summary: Cell surface proteins that bind lipoproteins with high affinity. Lipoprotein receptors in the liver and peripheral tissues mediate the regulation of plasma and cellular cholesterol metabolism and concentration. The receptors generally recognize the apolipoproteins of the lipoprotein complex, and binding is often a trigger for endocytosis.

Top Publications

  1. HOE H, Wessner D, Beffert U, Becker A, Matsuoka Y, Rebeck G. F-spondin interaction with the apolipoprotein E receptor ApoEr2 affects processing of amyloid precursor protein. Mol Cell Biol. 2005;25:9259-68 pubmed
    ..The reduction in APP beta-CTF was blocked by receptor-associated protein (RAP), an inhibitor of lipoprotein receptors, implicating ApoEr2 in the altered proteolysis of APP...
  2. Out R, Hoekstra M, de Jager S, de Vos P, van der Westhuyzen D, Webb N, et al. Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice. J Lipid Res. 2005;46:1172-81 pubmed
  3. Andreo U, Maillard P, Kalinina O, Walic M, Meurs E, Martinot M, et al. Lipoprotein lipase mediates hepatitis C virus (HCV) cell entry and inhibits HCV infection. Cell Microbiol. 2007;9:2445-56 pubmed
    ..These data provide new insight into mechanisms of HCV cell entry and suggest that LPL could modulate HCV infectivity in vivo. ..
  4. Herz J, Hui D. Lipoprotein receptors in the vascular wall. Curr Opin Lipidol. 2004;15:175-81 pubmed
    We will discuss the diverse roles of lipoprotein receptors that contribute to the maintenance and integrity of the vascular wall. Lipoprotein receptors function not only as transporters for cholesterol and other lipids...
  5. May P, Bock H, Herz J. Integration of endocytosis and signal transduction by lipoprotein receptors. Sci STKE. 2003;2003:PE12 pubmed
    ..Regulated proteolytic release of the intracellular domain of one of these lipoprotein receptors, the LDLR-related protein 1 (LRP1), has been described, along with the possible role of the released ..
  6. Ioka R, Kang M, Kamiyama S, Kim D, Magoori K, Kamataki A, et al. Expression cloning and characterization of a novel glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein, GPI-HBP1. J Biol Chem. 2003;278:7344-9 pubmed
    ..In situ hybridization revealed the accumulation of GPI-HBP1 transcripts in cardiac muscle cells, hepatic Kupffer cells and sinusoidal endothelium, and bronchial epithelium and alveolar macrophages in the lung. ..
  7. Benhayon D, Magdaleno S, Curran T. Binding of purified Reelin to ApoER2 and VLDLR mediates tyrosine phosphorylation of Disabled-1. Brain Res Mol Brain Res. 2003;112:33-45 pubmed
    ..These findings demonstrate that ApoER2 and VLDLR are essential for Reelin signaling and that no other receptor molecules can compensate for their role in mediating tyrosine phosphorylation of Dab1. ..
  8. Beffert U, Durudas A, Weeber E, Stolt P, Giehl K, Sweatt J, et al. Functional dissection of Reelin signaling by site-directed disruption of Disabled-1 adaptor binding to apolipoprotein E receptor 2: distinct roles in development and synaptic plasticity. J Neurosci. 2006;26:2041-52 pubmed
    ..Together, these findings emphasize the complexity of Reelin signaling in the adult brain, which likely requires multiple adaptor protein interactions with the intracellular domain of Apoer2. ..
  9. Beffert U, Weeber E, Durudas A, Qiu S, Masiulis I, Sweatt J, et al. Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor Apoer2. Neuron. 2005;47:567-79 pubmed
    ..Thus, alternative splicing of Apoer2, a novel component of the NMDA receptor complex, controls the modulation of NMDA receptor activity, synaptic neurotransmission, and memory by Reelin. ..

More Information


  1. Perez Garcia C, Tissir F, Goffinet A, Meyer G. Reelin receptors in developing laminated brain structures of mouse and human. Eur J Neurosci. 2004;20:2827-32 pubmed
    ..In sum, the receptor expression patterns are similar in the human and mouse cortical plate but differ in Cajal-Retzius and Purkinje cells, which in humans express additional components of the reelin-Dab1 pathway. ..
  2. Persaud D, Yousefi V, Haunerland N. Efficient isolation, purification, and characterization of the Helicoverpa zea VHDL receptor. Protein Expr Purif. 2003;32:260-4 pubmed
    ..Sufficient receptor protein has been derived for amino acid analysis, receptor-ligand and xenobiotic binding studies. ..
  3. Kaul D. Cholesterol-receptor-mediated genomics in health and disease. Trends Mol Med. 2003;9:442-9 pubmed
  4. Elner V. Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids. Trans Am Ophthalmol Soc. 2002;100:301-38 pubmed
    ..Diets rich in fish oil-derived omega-3 fatty acids, by enhancing acid lipase, may reduce RPE lipofuscin accumulation, RPE oxidative damage, and the development of ARMD. ..
  5. Bock H, Herz J. Reelin activates SRC family tyrosine kinases in neurons. Curr Biol. 2003;13:18-26 pubmed
    ..Based on genetic evidence gained from multiple strains of mutant mice with defects in Reelin signaling, we conclude that activation of SFKs is a normal part of the cellular Reelin response. ..
  6. Lee C, De Biasio A, Beglova N. Mode of interaction between beta2GPI and lipoprotein receptors suggests mutually exclusive binding of beta2GPI to the receptors and anionic phospholipids. Structure. 2010;18:366-76 pubmed publisher
    b>Lipoprotein receptors of the LDLR family serve as clearance receptors for beta2GPI and as signaling receptors for the beta2GPI/antibody complexes in antiphospholipid syndrome...
  7. Jaworska Wilczyńska M, Wilczynski G, Engel W, Strickland D, Weisgraber K, Askanas V. Three lipoprotein receptors and cholesterol in inclusion-body myositis muscle. Neurology. 2002;58:438-45 pubmed
    ..b>Lipoprotein receptors and cholesterol are known to play an important role in AbetaPP processing, Abeta production, and tau ..
  8. Lieb W, Zeller T, Mangino M, Götz A, Braund P, Wenzel J, et al. Lack of association of genetic variants in the LRP8 gene with familial and sporadic myocardial infarction. J Mol Med (Berl). 2008;86:1163-70 pubmed publisher
    ..In the WTCCC and the German MI Family studies, additional single-nucleotide polymorphisms in the LRP8 gene were analysed and displayed no evidence for association either. ..
  9. Herz J, Chen Y. Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci. 2006;7:850-9 pubmed
    ..The lipoprotein receptors that bind APOE have recently been recognized as pivotal components of the neuronal signalling machinery...
  10. Mayer H, Duit S, Hauser C, Schneider W, Nimpf J. Reconstitution of the Reelin signaling pathway in fibroblasts demonstrates that Dab1 phosphorylation is independent of receptor localization in lipid rafts. Mol Cell Biol. 2006;26:19-27 pubmed
  11. Poirier S, Mayer G, Benjannet S, Bergeron E, Marcinkiewicz J, Nassoury N, et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem. 2008;283:2363-72 pubmed
    ..Thus, this study demonstrates a more general effect of PCSK9 on the degradation of the LDLR family that emphasizes its major role in cholesterol and lipid homeostasis as well as brain development. ..
  12. Niu S, Renfro A, Quattrocchi C, Sheldon M, D ARCANGELO G. Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway. Neuron. 2004;41:71-84 pubmed
    ..Thus, the same signaling pathway controls both neuronal migration and dendrite maturation. ..
  13. White T, Berny M, Tucker E, Urbanus R, de Groot P, Fernandez J, et al. Protein C supports platelet binding and activation under flow: role of glycoprotein Ib and apolipoprotein E receptor 2. J Thromb Haemost. 2008;6:995-1002 pubmed publisher
    ..These findings imply that protein C and APC may directly promote cell signaling in other cells by binding to ApoER2 and/or GPIbalpha. ..
  14. Beglov D, Lee C, De Biasio A, Kozakov D, Brenke R, Vajda S, et al. Structural insights into recognition of beta2-glycoprotein I by the lipoprotein receptors. Proteins. 2009;77:940-9 pubmed publisher
    ..The ligand-binding domains of the lipoprotein receptors consist of multiple homologous LA modules connected by flexible linkers...
  15. Herz J, Chen Y, Masiulis I, Zhou L. Expanding functions of lipoprotein receptors. J Lipid Res. 2009;50 Suppl:S287-92 pubmed publisher
    b>Lipoprotein receptors are evolutionarily ancient proteins that are expressed on the surface of many cell types...
  16. Yamanouchi J, Takatori A, Nishida E, Kawamura S, Yoshikawa Y. Expression of lipoprotein receptors in the aortic walls of diabetic APA hamsters. Exp Anim. 2002;51:33-41 pubmed
    ..Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the ..
  17. Kamikura D, Cooper J. Lipoprotein receptors and a disabled family cytoplasmic adaptor protein regulate EGL-17/FGF export in C. elegans. Genes Dev. 2003;17:2798-811 pubmed
    ..b>Lipoprotein receptors are transmembrane proteins best known for their roles in endocytosis...
  18. Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, et al. Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem. 2003;278:41624-30 pubmed
    ..Finally, by correlating expression of HCV receptors and infectivity, we suggest that, besides CD81 and SR-B1, additional hepatocyte-specific co-factor(s) are necessary for HCV entry. ..
  19. Stolt P, Bock H. Modulation of lipoprotein receptor functions by intracellular adaptor proteins. Cell Signal. 2006;18:1560-71 pubmed
    ..b>Lipoprotein receptors exert these diverse biological functions by acting as cellular uptake receptors or by inducing ..
  20. Pennings M, Derksen R, Urbanus R, Tekelenburg W, Hemrika W, de Groot P. Platelets express three different splice variants of ApoER2 that are all involved in signaling. J Thromb Haemost. 2007;5:1538-44 pubmed
    ..All splice variants were shown to be functional by translocation upon stimulation with dimeric beta2-GPI. All three splice variants express LDL-binding domain 1. ..
  21. Beffert U, Nematollah Farsian F, Masiulis I, Hammer R, Yoon S, Giehl K, et al. ApoE receptor 2 controls neuronal survival in the adult brain. Curr Biol. 2006;16:2446-52 pubmed
    ..These findings raise the possibility that ApoE and its receptors cooperatively regulate common mechanisms that are essential to neuronal survival in the adult brain. ..
  22. Qiu S, Korwek K, Weeber E. A fresh look at an ancient receptor family: emerging roles for low density lipoprotein receptors in synaptic plasticity and memory formation. Neurobiol Learn Mem. 2006;85:16-29 pubmed
    The well-known family of low-density lipoprotein receptors represents a collection of ancient membrane receptors that have been remarkably conserved throughout evolution...
  23. Shan L, Pang L, Zhang R, Murgolo N, Lan H, Hedrick J. PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide. Biochem Biophys Res Commun. 2008;375:69-73 pubmed publisher
    ..These data demonstrate that while PCSK9 binds several receptors via its EGF-A binding domain, additional contacts with other receptor domains are also involved. ..
  24. Hack I, Hellwig S, Junghans D, Brunne B, Bock H, Zhao S, et al. Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons. Development. 2007;134:3883-91 pubmed
    Reelin, its lipoprotein receptors [very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (ApoER2; also known as Lrp8)], and the cytoplasmic adaptor protein disabled 1 (Dab1) are important for the correct formation ..
  25. Zhou Y, Zhang J, King M. Xenopus autosomal recessive hypercholesterolemia protein couples lipoprotein receptors with the AP-2 complex in oocytes and embryos and is required for vitellogenesis. J Biol Chem. 2003;278:44584-92 pubmed
    ..its expression pattern in development and used pull-down experiments to assess interactions between xARH, lipoprotein receptors and proteins in embryo extracts...
  26. Wadsack C, Tabano S, Maier A, Hiden U, Alvino G, Cozzi V, et al. Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition. Am J Physiol Endocrinol Metab. 2007;292:E476-84 pubmed
    ..28 +/- 0.20, P = 0.002). We conclude that LDL-R and SR-BI levels are altered in IUGR pregnancies. These differences were associated with changes in LDL, but not HDL, mobility and cholesterol concentration in maternal circulation. ..
  27. Shen G, Li L, Girelli D, Seidelmann S, Rao S, Fan C, et al. An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. Am J Hum Genet. 2007;81:780-91 pubmed
    ..This extensive study, involving multiple independent populations, provides the first evidence that genetic variants in LRP8 may contribute to the development of premature and familial CAD and MI. ..
  28. Beffert U, Stolt P, Herz J. Functions of lipoprotein receptors in neurons. J Lipid Res. 2004;45:403-9 pubmed
  29. Pires L, Hegg R, Valduga C, Graziani S, Rodrigues D, Maranhão R. Use of cholesterol-rich nanoparticles that bind to lipoprotein receptors as a vehicle to paclitaxel in the treatment of breast cancer: pharmacokinetics, tumor uptake and a pilot clinical study. Cancer Chemother Pharmacol. 2009;63:281-7 pubmed publisher
  30. Zhao S, Chai X, Bock H, Brunne B, Forster E, Frotscher M. Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for Reelin and Disabled 1. J Comp Neurol. 2006;495:1-9 pubmed
    ..findings show that Reelin from other brain regions can substitute for the loss of hippocampal Reelin and that rescue of the reeler phenotype observed in our coculture studies is mediated via lipoprotein receptors for Reelin and Dab1.
  31. Andersen O, Yeung C, Vorum H, Wellner M, Andreassen T, Erdmann B, et al. Essential role of the apolipoprotein E receptor-2 in sperm development. J Biol Chem. 2003;278:23989-95 pubmed
  32. Scarselli E, Ansuini H, Cerino R, Roccasecca R, Acali S, Filocamo G, et al. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 2002;21:5017-25 pubmed
    ..Finally, E2 recognition by SR-BI was competed out in an isolate-specific manner both on the hepatoma cell line and on the human SR-BI-transfected cell line by an anti-HVR1 monoclonal antibody. ..
  33. Yang X, Banerjee Y, Fernandez J, Deguchi H, Xu X, Mosnier L, et al. Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells. Proc Natl Acad Sci U S A. 2009;106:274-9 pubmed publisher
    ..Thus, we propose that ligation of ApoER2 by APC signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and inactivation of GSK3beta, thereby contributing to APC's beneficial effects on cells. ..
  34. Andersen O, Willnow T. Lipoprotein receptors in Alzheimer's disease. Trends Neurosci. 2006;29:687-94 pubmed
    b>Lipoprotein receptors have important roles in pathological processes that lead to Alzheimer's disease (AD)...
  35. Yen F, Roitel O, Bonnard L, Notet V, Pratte D, Stenger C, et al. Lipolysis stimulated lipoprotein receptor: a novel molecular link between hyperlipidemia, weight gain, and atherosclerosis in mice. J Biol Chem. 2008;283:25650-9 pubmed publisher
  36. Beigneux A, Davies B, Gin P, Weinstein M, Farber E, Qiao X, et al. Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metab. 2007;5:279-91 pubmed
    ..Expression of GPIHBP1 in cultured cells confers the ability to bind both LpL and chylomicrons. These studies strongly suggest that GPIHBP1 is an important platform for the LpL-mediated processing of chylomicrons in capillaries. ..
  37. Gälman C, Angelin B, Rudling M. Prolonged stimulation of the adrenals by corticotropin suppresses hepatic low-density lipoprotein and high-density lipoprotein receptors and increases plasma cholesterol. Endocrinology. 2002;143:1809-16 pubmed
    ..Hypothetically, this novel mechanism would further promote channeling of cholesterol to the adrenals in situations of prolonged stress. ..
  38. Urbanus R, Pennings M, Derksen R, de Groot P. Platelet activation by dimeric beta2-glycoprotein I requires signaling via both glycoprotein Ibalpha and apolipoprotein E receptor 2'. J Thromb Haemost. 2008;6:1405-12 pubmed publisher
    ..We show that dimeric beta(2)-GPI signals via two distinct pathways in platelets, both of which are required for platelet activation. Abrogation of either signal results in loss of activation. ..
  39. Veinbergs I, Van Uden E, Mallory M, Alford M, McGiffert C, DeTeresa R, et al. Role of apolipoprotein E receptors in regulating the differential in vivo neurotrophic effects of apolipoprotein E. Exp Neurol. 2001;170:15-26 pubmed
  40. Tacken P, Hofker M, Havekes L, van Dijk K. Living up to a name: the role of the VLDL receptor in lipid metabolism. Curr Opin Lipidol. 2001;12:275-9 pubmed
  41. Silver D, Wang N, Xiao X, Tall A. High density lipoprotein (HDL) particle uptake mediated by scavenger receptor class B type 1 results in selective sorting of HDL cholesterol from protein and polarized cholesterol secretion. J Biol Chem. 2001;276:25287-93 pubmed
    ..A distinct process not mediated by SR-BI is involved in uptake and degradation of apoE-free HDL in hepatocytes. ..
  42. Herz J. Lipoprotein receptors: beacons to neurons?. Trends Neurosci. 2001;24:193-5 pubmed
    b>Lipoprotein receptors were originally considered simply as cellular transporters for cholesterol and other lipids. This view is rapidly changing...
  43. Korschineck I, Ziegler S, Breuss J, Lang I, Lorenz M, Kaun C, et al. Identification of a novel exon in apolipoprotein E receptor 2 leading to alternatively spliced mRNAs found in cells of the vascular wall but not in neuronal tissue. J Biol Chem. 2001;276:13192-7 pubmed
  44. Rebeck G, Moir R, Mui S, Strickland D, Tanzi R, Hyman B. Association of membrane-bound amyloid precursor protein APP with the apolipoprotein E receptor LRP. Brain Res Mol Brain Res. 2001;87:238-45 pubmed
    ..We propose that full-length APP can transiently interact with the receptor LRP on the cell surface, affecting the processing and intracellular transport of APP. ..
  45. Brandes C, Kahr L, Stockinger W, Hiesberger T, Schneider W, Nimpf J. Alternative splicing in the ligand binding domain of mouse ApoE receptor-2 produces receptor variants binding reelin but not alpha 2-macroglobulin. J Biol Chem. 2001;276:22160-9 pubmed
  46. Wang L, Wang X, Laird N, Zuckerman B, Stubblefield P, Xu X. Polymorphism in maternal LRP8 gene is associated with fetal growth. Am J Hum Genet. 2006;78:770-777 pubmed publisher
    ..05). In conclusion, results from the two independent samples of black women provide consistent evidence that SNP rs2297660 in LRP8 is associated with fetal growth. ..
  47. Garnis C, Campbell J, Davies J, Macaulay C, Lam S, Lam W. Involvement of multiple developmental genes on chromosome 1p in lung tumorigenesis. Hum Mol Genet. 2005;14:475-82 pubmed
    ..Importantly, this implication of pathways known only to be activated in fetal lung development lends support to the proposed model of lung cancer ontology whereby tumors arise from dysregulated pleuripotent stem cells. ..
  48. Hansen B, Melkko J, Smedsrød B. Serum is a rich source of ligands for the scavenger receptor of hepatic sinusoidal endothelial cells. Mol Cell Biochem. 2002;229:63-72 pubmed
    ..The inhibitory power of pre-heated serum is particularly great. For this reason pre-heated serum should be used with caution in studies of SR in SEC. ..
  49. Barr A, MacLaurin S, Semenova S, Fish K, Markou A. Altered performance of reelin-receptor ApoER2 deficient mice on spatial tasks using the Barnes maze. Behav Neurosci. 2007;121:1101-5 pubmed
    ..ApoER2 knockout mice also displayed altered use of specific search strategies and relationship of these strategies to errors made on the maze. ..
  50. Luque J, Morante Oria J, Fairen A. Localization of ApoER2, VLDLR and Dab1 in radial glia: groundwork for a new model of reelin action during cortical development. Brain Res Dev Brain Res. 2003;140:195-203 pubmed
    ..Here we provide evidence that the reelin receptor machinery, including the lipoprotein receptors ApoER2 and VLDLR along with the cytoplasmic adaptor protein Dab1, is located in radial glia precursors ..
  51. Tai E, Adiconis X, Ordovas J, Carmena Ramon R, Real J, Corella D, et al. Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia. Clin Genet. 2003;63:53-8 pubmed
  52. Stangl H, Graf G, Yu L, Cao G, Wyne K. Effect of estrogen on scavenger receptor BI expression in the rat. J Endocrinol. 2002;175:663-72 pubmed
    ..In the liver, the decrease in SR-BI is dependent on the estrogen-induced increase in LDLR activity, and in the adrenal glands, ACTH is required for the estrogen-associated increase in expression of SR-BI. ..
  53. Thornalley P. Methods for studying the binding of advanced glycated proteins to receptors for advanced glycation endproducts (AGE receptors). Methods Mol Biol. 2002;196:49-62 pubmed