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Gene Review

LRP8  -  low density lipoprotein receptor-related...

Homo sapiens

Synonyms: APOER2, Apolipoprotein E receptor 2, HSZ75190, LRP-8, Low-density lipoprotein receptor-related protein 8, ...
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Disease relevance of LRP8

  • These results demonstrate that dimeric beta 2GPI induces increased platelet adhesion and thrombus formation, which depends on activation via apoER2' [1].
  • We found significant association between SNP rs2297660 in the LRP8 gene and birth weight [2].
  • Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Y and CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma, NT-2 precursor cells and IMR-32 neuroblastoma cells [3].

Psychiatry related information on LRP8


High impact information on LRP8

  • Apoer2: a reelin receptor to remember [5].
  • In conclusion, results from the two independent samples of black women provide consistent evidence that SNP rs2297660 in LRP8 is associated with fetal growth [2].
  • Furthermore, ectopic expression of DVL1, LRP8 and Notch2 in malignant lung tissue validates the biological impact of these genetic alterations [6].
  • ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain [7].
  • DAB1 and Reelin Effects on Amyloid Precursor Protein and ApoE Receptor 2 Trafficking and Processing [8].

Biological context of LRP8


Anatomical context of LRP8


Associations of LRP8 with chemical compounds

  • Then, using a homology cloning approach and degenerate PCR primers to amplify the conserved Cys-rich binding domain of the LDL-R family, this receptor was identified as LRP8 (formerly termed, apoER2), a newly described brain protein with several splice variants [9].
  • Phosphatidylinositol (PI) 3-kinase inhibitors suppressed the apoE effect, while apoE receptor 2 (apoER2) was tyrosine phosphorylated [15].
  • This may indicate a role of LRP8 in cholesterol delivery to steriodogenic cells [16].

Physical interactions of LRP8

  • DeltaV did not associate with apoER2'. We conclude that domain V is involved in both binding beta(2)GPI to anionic PL and in interaction with apoER2' and subsequent activation of platelets [17].
  • This finding explains how the Dab1 PTB domain can simultaneously bind PI and the ApoER2 tail [18].

Regulatory relationships of LRP8

  • Adhesion of platelets to dimerized beta(2)GPI was completely inhibited by the addition of soluble forms of both apoER2' and GPIbalpha, and the addition of receptor-associated protein and the removal of GPIbalpha from the platelet surface [19].

Other interactions of LRP8


Analytical, diagnostic and therapeutic context of LRP8

  • By means of splice variant-specific in situ hybridization, we could confirm that apoEr2 mRNA is abundantly expressed in brain tissue and, with exception of the newly identified ligand binding domain, all mRNA splice variants exhibited a similar expression pattern [13].
  • When mammalian expression vectors for eight potential protein isoforms were transfected into LDL-receptor-deficient Chinese hamster ovary cells, the proteins were all expressed on the cell surface, as detected by immunoblotting of cell extracts with a specific antipeptide antiserum to apoER2 before and after treatment of intact cells with pronase [22].
  • It was widely assumed that other closely related members of the LDL-R gene family would have similar functions, but recent experimental evidence has revealed that one such protein, apolipoprotein E receptor 2 (apoER2), has a critical role as an "outside-in" signal transducer in the brain [23].


  1. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. Lutters, B.C., Derksen, R.H., Tekelenburg, W.L., Lenting, P.J., Arnout, J., de Groot, P.G. J. Biol. Chem. (2003) [Pubmed]
  2. Polymorphism in Maternal LRP8 Gene Is Associated with Fetal Growth. Wang, L., Wang, X., Laird, N., Zuckerman, B., Stubblefield, P., Xu, X. Am. J. Hum. Genet. (2006) [Pubmed]
  3. Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction. Thilakawardhana, S., Everett, D.M., Murdock, P.R., Dingwall, C., Owen, J.S. Neurobiol. Aging (2005) [Pubmed]
  4. Low-density lipoprotein receptor-related protein 8 (apolipoprotein E receptor 2) gene polymorphisms in Alzheimer's disease. Ma, S.L., Ng, H.K., Baum, L., Pang, J.C., Chiu, H.F., Woo, J., Tang, N.L., Lam, L.C. Neurosci. Lett. (2002) [Pubmed]
  5. Apoer2: a reelin receptor to remember. D'Arcangelo, G. Neuron (2005) [Pubmed]
  6. Involvement of multiple developmental genes on chromosome 1p in lung tumorigenesis. Garnis, C., Campbell, J., Davies, J.J., Macaulay, C., Lam, S., Lam, W.L. Hum. Mol. Genet. (2005) [Pubmed]
  7. ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain. Beffert, U., Nematollah Farsian, F., Masiulis, I., Hammer, R.E., Yoon, S.O., Giehl, K.M., Herz, J. Curr. Biol. (2006) [Pubmed]
  8. DAB1 and Reelin Effects on Amyloid Precursor Protein and ApoE Receptor 2 Trafficking and Processing. Hoe, H.S., Tran, T.S., Matsuoka, Y., Howell, B.W., Rebeck, G.W. J. Biol. Chem. (2006) [Pubmed]
  9. Identification and characterization of LRP8 (apoER2) in human blood platelets. Riddell, D.R., Vinogradov, D.V., Stannard, A.K., Chadwick, N., Owen, J.S. J. Lipid Res. (1999) [Pubmed]
  10. Expression and alternate splicing of apolipoprotein E receptor 2 in brain. Clatworthy, A.E., Stockinger, W., Christie, R.H., Schneider, W.J., Nimpf, J., Hyman, B.T., Rebeck, G.W. Neuroscience (1999) [Pubmed]
  11. Interaction of beta2-glycoprotein I with members of the low density lipoprotein receptor family. Pennings, M.T., van Lummel, M., Derksen, R.H., Urbanus, R.T., Romijn, R.A., Lenting, P.J., de Groot, P.G. J. Thromb. Haemost. (2006) [Pubmed]
  12. The transmembrane domain and PXXP motifs of ApoE receptor 2 exclude it from carrying out clathrin-mediated endocytosis. Sun, X.M., Soutar, A.K. J. Biol. Chem. (2003) [Pubmed]
  13. 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. Korschineck, I., Ziegler, S., Breuss, J., Lang, I., Lorenz, M., Kaun, C., Ambros, P.F., Binder, B.R. J. Biol. Chem. (2001) [Pubmed]
  14. Apolipoprotein E receptor 2 is involved in neuritic plaque formation in APP sw mice. Motoi, Y., Itaya, M., Mori, H., Mizuno, Y., Iwasaki, T., Hattori, H., Haga, S., Ikeda, K. Neurosci. Lett. (2004) [Pubmed]
  15. Apolipoprotein E (apoE) isoforms differentially induce nitric oxide production in endothelial cells. Sacre, S.M., Stannard, A.K., Owen, J.S. FEBS Lett. (2003) [Pubmed]
  16. Expression of mRNA of lipoprotein receptor related protein 8, low density lipoprotein receptor, and very low density lipoprotein receptor in bovine ovarian cells during follicular development and corpus luteum formation and regression. Argov, N., Sklan, D. Mol. Reprod. Dev. (2004) [Pubmed]
  17. The binding site in {beta}2-glycoprotein I for ApoER2' on platelets is located in domain V. van Lummel, M., Pennings, M.T., Derksen, R.H., Urbanus, R.T., Lutters, B.C., Kaldenhoven, N., de Groot, P.G. J. Biol. Chem. (2005) [Pubmed]
  18. Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes. Stolt, P.C., Jeon, H., Song, H.K., Herz, J., Eck, M.J., Blacklow, S.C. Structure (Camb.) (2003) [Pubmed]
  19. Platelet adhesion to dimeric beta-glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ibalpha and apolipoprotein E receptor 2'. Pennings, M.T., Derksen, R.H., VAN Lummel, M., Adelmeijer, J., Vanhoorelbeke, K., Urbanus, R.T., Lisman, T., DE Groot, P.G. J. Thromb. Haemost. (2007) [Pubmed]
  20. Close encounters with apolipoprotein E receptors. Yamamoto, T., Bujo, H. Curr. Opin. Lipidol. (1996) [Pubmed]
  21. Enhanced APOE2 transmission rates in families with autistic probands. Persico, A.M., D'Agruma, L., Zelante, L., Militerni, R., Bravaccio, C., Schneider, C., Melmed, R., Trillo, S., Montecchi, F., Elia, M., Palermo, M., Rabinowitz, D., Pascucci, T., Puglisi-Allegra, S., Reichelt, K.L., Muscarella, L., Guarnieri, V., Melgari, J.M., Conciatori, M., Keller, F. Psychiatr. Genet. (2004) [Pubmed]
  22. Expression in vitro of alternatively spliced variants of the messenger RNA for human apolipoprotein E receptor-2 identified in human tissues by ribonuclease protection assays. Sun, X.M., Soutar, A.K. Eur. J. Biochem. (1999) [Pubmed]
  23. Localization of apolipoprotein E receptor 2 to caveolae in the plasma membrane. Riddell, D.R., Sun, X.M., Stannard, A.K., Soutar, A.K., Owen, J.S. J. Lipid Res. (2001) [Pubmed]
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