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Gene Review

Lrp2  -  low density lipoprotein receptor-related...

Mus musculus

Synonyms: AI315343, AW536255, D230004K18Rik, Glycoprotein 330, Gp330, ...
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Disease relevance of Lrp2


High impact information on Lrp2

  • In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females [6].
  • (2005) show that resistance (insensitivity) to sex steroid hormones is encountered in animals lacking megalin [7].
  • We show that 25-(OH) vitamin D3 in complex with its plasma carrier, the vitamin D-binding protein, is filtered through the glomerulus and reabsorbed in the proximal tubules by the endocytic receptor megalin [3].
  • These findings demonstrate a pathway whereby circulating lysosomal enzymes are continuously filtered in glomeruli, reabsorbed by megalin-mediated endocytosis, and transferred into lysosomes to exert their function, providing a major source of enzymes to PCT [8].
  • Thus, impaired protein endocytosis caused by invalidation of ClC-5 primarily reflects a trafficking defect of megalin and cubilin in PTC [9].

Chemical compound and disease context of Lrp2


Biological context of Lrp2

  • We used mice with complete or conditional megalin gene inactivation in the embryo to demonstrate that expression of megalin in the neuroepithelium but not in the yolk sac is crucial for brain development [1].
  • The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine [2].
  • The present study examines the effect of RAP gene disruption on megalin expression and subcellular distribution in the proximal tubule as well as the effect on tubular protein reabsorption [12].
  • METHODS: We used genome-wide expression profiling by microarray technology to detect changes in the gene expression pattern in megalin knockout mouse kidneys and to uncover some of the renal pathways affected by megalin deficiency [13].
  • RESULTS: Alterations were identified in several (patho)physiologic processes in megalin-deficient kidneys including the renal vitamin D metabolism, transforming growth factor (TGF)-beta1 signal transduction, lipid transport and heavy metal detoxification [13].

Anatomical context of Lrp2


Associations of Lrp2 with chemical compounds

  • gp330/megalin, a member of the low density lipoprotein (LDL) receptor gene family, is expressed on the apical surfaces of epithelial tissues, including the neuroepithelium, where it mediates the endocytic uptake of diverse macromolecules, such as cholesterol-carrying lipoproteins, proteases, and antiproteinases [4].
  • Evidence for an essential role of megalin in transepithelial transport of retinol [16].
  • In this report, we show that the low density lipoprotein receptor (LDLR) gene family member megalin/glycoprotein (gp) 330 is capable of binding and mediating the cellular uptake and degradation of Lp(a) in vitro [17].
  • Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis [18].
  • A major effect of megalin deficiency, however, was evident in retinyl ester levels in the liver (P < 0.05), which were approximately 37% lower than those in megalin(lox/lox) controls (P < 0.05, Student's t test) during the 84-d period of dietary VA deprivation [18].
  • TGF-beta, intercellular adhesion molecule, vascular cellular adhesion molecule, endothelin-1, and cell proliferation were high in megalin-positive cells, whereas apoptosis, heat-shock protein 25, and osteopontin were enhanced in megalin-deficient cells [19].

Physical interactions of Lrp2


Co-localisations of Lrp2


Regulatory relationships of Lrp2


Other interactions of Lrp2


Analytical, diagnostic and therapeutic context of Lrp2


  1. LRP2/megalin is required for patterning of the ventral telencephalon. Spoelgen, R., Hammes, A., Anzenberger, U., Zechner, D., Andersen, O.M., Jerchow, B., Willnow, T.E. Development (2005) [Pubmed]
  2. Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M. Faber, K., Hvidberg, V., Moestrup, S.K., Dahlbäck, B., Nielsen, L.B. Mol. Endocrinol. (2006) [Pubmed]
  3. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Nykjaer, A., Dragun, D., Walther, D., Vorum, H., Jacobsen, C., Herz, J., Melsen, F., Christensen, E.I., Willnow, T.E. Cell (1999) [Pubmed]
  4. Defective forebrain development in mice lacking gp330/megalin. Willnow, T.E., Hilpert, J., Armstrong, S.A., Rohlmann, A., Hammer, R.E., Burns, D.K., Herz, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. ClC-5 Does Not Affect Megalin Expression and Function in the Thyroid. Maritzen, T., Lisi, S., Botta, R., Pinchera, A., Fanelli, G., Viacava, P., Marcocci, C., Marinò, M. Thyroid (2006) [Pubmed]
  6. Role of endocytosis in cellular uptake of sex steroids. Hammes, A., Andreassen, T.K., Spoelgen, R., Raila, J., Hubner, N., Schulz, H., Metzger, J., Schweigert, F.J., Luppa, P.B., Nykjaer, A., Willnow, T.E. Cell (2005) [Pubmed]
  7. "Bound" to work: the free hormone hypothesis revisited. Adams, J.S. Cell (2005) [Pubmed]
  8. Endocytosis provides a major alternative pathway for lysosomal biogenesis in kidney proximal tubular cells. Nielsen, R., Courtoy, P.J., Jacobsen, C., Dom, G., Lima, W.R., Jadot, M., Willnow, T.E., Devuyst, O., Christensen, E.I. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  9. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Christensen, E.I., Devuyst, O., Dom, G., Nielsen, R., Van der Smissen, P., Verroust, P., Leruth, M., Guggino, W.B., Courtoy, P.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  10. Thyroid dysfunction in megalin deficient mice. Lisi, S., Segnani, C., Mattii, L., Botta, R., Marcocci, C., Dolfi, A., McCluskey, R.T., Pinchera, A., Bernardini, N., Marinò, M. Mol. Cell. Endocrinol. (2005) [Pubmed]
  11. Glycoprotein 330/low density lipoprotein receptor-related protein-2 mediates endocytosis of low density lipoproteins via interaction with apolipoprotein B100. Stefansson, S., Chappell, D.A., Argraves, K.M., Strickland, D.K., Argraves, W.S. J. Biol. Chem. (1995) [Pubmed]
  12. Receptor-associated protein is important for normal processing of megalin in kidney proximal tubules. Birn, H., Vorum, H., Verroust, P.J., Moestrup, S.K., Christensen, E.I. J. Am. Soc. Nephrol. (2000) [Pubmed]
  13. Expression profiling confirms the role of endocytic receptor megalin in renal vitamin D3 metabolism. Hilpert, J., Wogensen, L., Thykjaer, T., Wellner, M., Schlichting, U., Orntoft, T.F., Bachmann, S., Nykjaer, A., Willnow, T.E. Kidney Int. (2002) [Pubmed]
  14. Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein. Maurer, M.E., Cooper, J.A. J. Cell. Sci. (2005) [Pubmed]
  15. Low-density lipoprotein receptor-related protein (LRP)-2/megalin is transiently expressed in a subpopulation of neural progenitors in the embryonic mouse spinal cord. Wicher, G., Larsson, M., Rask, L., Aldskogius, H. J. Comp. Neurol. (2005) [Pubmed]
  16. Evidence for an essential role of megalin in transepithelial transport of retinol. Christensen, E.I., Moskaug, J.O., Vorum, H., Jacobsen, C., Gundersen, T.E., Nykjaer, A., Blomhoff, R., Willnow, T.E., Moestrup, S.K. J. Am. Soc. Nephrol. (1999) [Pubmed]
  17. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro. Niemeier, A., Willnow, T., Dieplinger, H., Jacobsen, C., Meyer, N., Hilpert, J., Beisiegel, U. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  18. Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis. Raila, J., Willnow, T.E., Schweigert, F.J. J. Nutr. (2005) [Pubmed]
  19. Abrogation of protein uptake through megalin-deficient proximal tubules does not safeguard against tubulointerstitial injury. Theilig, F., Kriz, W., Jerichow, T., Schrade, P., Hähnel, B., Willnow, T., Le Hir, M., Bachmann, S. J. Am. Soc. Nephrol. (2007) [Pubmed]
  20. Mutually dependent localization of megalin and Dab2 in the renal proximal tubule. Nagai, J., Christensen, E.I., Morris, S.M., Willnow, T.E., Cooper, J.A., Nielsen, R. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  21. Apolipoprotein M - a novel player in high-density lipoprotein metabolism and atherosclerosis. Dahlbäck, B., Nielsen, L.B. Curr. Opin. Lipidol. (2006) [Pubmed]
  22. Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin. Gburek, J., Birn, H., Verroust, P.J., Goj, B., Jacobsen, C., Moestrup, S.K., Willnow, T.E., Christensen, E.I. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  23. Megalin functions as an endocytic sonic hedgehog receptor. McCarthy, R.A., Barth, J.L., Chintalapudi, M.R., Knaak, C., Argraves, W.S. J. Biol. Chem. (2002) [Pubmed]
  24. Targeted prevention of renal accumulation and toxicity of gentamicin by aminoglycoside binding receptor antagonists. Watanabe, A., Nagai, J., Adachi, Y., Katsube, T., Kitahara, Y., Murakami, T., Takano, M. Journal of controlled release : official journal of the Controlled Release Society. (2004) [Pubmed]
  25. Linking receptor-mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule. Zou, Z., Chung, B., Nguyen, T., Mentone, S., Thomson, B., Biemesderfer, D. J. Biol. Chem. (2004) [Pubmed]
  26. Intraperitoneal administration of recombinant receptor-associated protein causes phosphaturia via an alteration in subcellular distribution of the renal sodium phosphate co-transporter. Yamagata, M., Ozono, K., Hashimoto, Y., Miyauchi, Y., Kondou, H., Michigami, T. J. Am. Soc. Nephrol. (2005) [Pubmed]
  27. In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31-->q32.1 and porcine chromosome region 15q22-->q24. Chowdhary, B.P., Lundgren, S., Johansson, M., Hjälm, G., Akerström, G., Gustavsson, I., Rask, L. Cytogenet. Cell Genet. (1995) [Pubmed]
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