The LDL receptor‐related protein (LRP) family: An old family of proteins with new physiological functions

References

• Goldstein J. L., DeBose‐Boyd R. A., Brown M. S. Protein sensors for membrane sterols. Cell 2006; 124: 35–46
   PubMed Web of Science ®Google Scholar
• Horton J. D., Goldstein J. L., Brown M. S. SREBPs: transcriptional mediators of lipid homeostasis. Cold Spring Harb Symp Quant Biol 2002; 67: 491–8
   PubMedGoogle Scholar
• Herz J., Hamann U., Rogne S., Myklebost O., Gausepohl H., Stanley K. K. Surface location and high affinity for calcium of a 500‐kd liver membrane protein closely related to the LDL‐receptor suggest a physiological role as lipoprotein receptor. EMBO J 1988; 7: 4119–27
   PubMed Web of Science ®Google Scholar
• Herz J., Hui D. Y. Lipoprotein receptors in the vascular wall. Curr Opin Lipidol 2004; 15: 175–81
   PubMed Web of Science ®Google Scholar
• Boucher P., Gotthardt M., Li W. P., Anderson R. G., Herz J. LRP: role in vascular wall integrity and protection from atherosclerosis. Science 2003; 300: 329–32
   PubMed Web of Science ®Google Scholar
• Loukinova E., Ranganathan S., Kuznetsov S., Gorlatova N., Migliorini M. M., Loukinov D., et al. Platelet‐derived growth factor (PDGF)‐induced tyrosine phosphorylation of the low density lipoprotein receptor‐related protein (LRP). Evidence for integrated co‐receptor function betwenn LRP and the PDGF. J Biol Chem 2002; 277: 15499–506
   PubMed Web of Science ®Google Scholar
• Boucher P., Liu P., Gotthardt M., Hiesberger T., Anderson R. G., Herz J. Platelet‐derived growth factor mediates tyrosine phosphorylation of the cytoplasmic domain of the low Density lipoprotein receptor‐related protein in caveolae. J Biol Chem 2002; 277: 15507–13
   PubMed Web of Science ®Google Scholar
• Willnow T. E., Hilpert J., Armstrong S. A., Rohlmann A., Hammer R. E., Burns D. K., et al. Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci U S A 1996; 93: 8460–4
   PubMed Web of Science ®Google Scholar
• McCarthy R. A., Argraves W. S. Megalin and the neurodevelopmental biology of sonic hedgehog and retinol. J Cell Sci 2003; 116: 955–60
   PubMed Web of Science ®Google Scholar
• Spoelgen R., Hammes A., Anzenberger U., Zechner D., Andersen O. M., Jerchow B., et al. LRP2/megalin is required for patterning of the ventral telencephalon. Development 2005; 132: 405–14
   PubMed Web of Science ®Google Scholar
• Stolt P. C., Bock H. H. Modulation of lipoprotein receptor functions by intracellular adaptor proteins. Cell Signal 2006; 18: 1560–71
   PubMed Web of Science ®Google Scholar
• D'Arcangelo G. Apoer2: a reelin receptor to remember. Neuron 2005; 47: 471–3
   PubMed Web of Science ®Google Scholar
• Herz J., Strickland D. K. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest 2001; 108: 779–84
   PubMed Web of Science ®Google Scholar
• May P., Herz J. LDL receptor‐related proteins in neurodevelopment. Traffic 2003; 4: 291–301
   PubMed Web of Science ®Google Scholar
• Herz J., Clouthier D. E., Hammer R. E. LDL receptor‐related protein internalizes and degrades uPA‐PAI‐1 complexes and is essential for embryo implantation. Cell 1992; 71: 411–21
   PubMed Web of Science ®Google Scholar
• Lillis A. P., Mikhailenko I., Strickland D. K. Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability. J Thromb Haemost 2005; 3: 1884–93
   PubMed Web of Science ®Google Scholar
• Battegay E. J., Raines E. W., Seifert R. A., Bowen‐Pope D. F., Ross R. TGF‐beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 1990; 63: 515–24
   PubMed Web of Science ®Google Scholar
• Ihn H. Pathogenesis of fibrosis: role of TGF‐beta and CTGF. Curr Opin Rheumatol 2002; 14: 681–5
   PubMed Web of Science ®Google Scholar
• Taylor L. M., Khachigian L. M. Induction of platelet‐derived growth factor B‐chain expression by transforming growth factor‐beta involves transactivation by Smads. J Biol Chem 2000; 275: 16709–16
   PubMed Web of Science ®Google Scholar
• Huang S. S., Leal S. M., Chen C‐L., Liu I. H., Huang J. S. Identification of insulin receptor substrate proteins as key molecules for the TbetaR‐V/LRP‐1‐mediated growth inhibitory signaling cascade in epithelial and myeloid cells. FASEB J 2004; 18: 1719–21
   PubMed Web of Science ®Google Scholar
• Nassar T., Akkawi S., Shina A., Haj‐Yehia A., Bdeir K., Tarshis M., et al. In vitro and in vivo effects of tPA and PAI‐1 on blood vessel tone. Blood 2004; 103: 897–902
   PubMed Web of Science ®Google Scholar
• Yepes M., Sandkvist M., Moore E. G., Bugge T. H., Strickland D. K., Lawrence D. A. Tissue‐type plasminogen activator induces opening of the blood‐brain barrier via the LDL receptor‐related protein. J Clin Invest 2003; 112: 1533–40
   PubMed Web of Science ®Google Scholar
• Akkawi S., Nassar T., Tarshis M., Cines D. B., Higazi A. A. LRP and {alpha}vbeta3 mediate tPA activation of smooth muscle cells. Am J Physiol Heart Circ Physiol 2006; 291: H1351–9
   PubMed Web of Science ®Google Scholar
• Bu G., Maksymovitch E. A., Geuze H., Schwartz A. L. Subcellular localization and endocytic function of low density lipoprotein receptor‐related protein in human glioblastoma cells. J Biol Chem 1994; 269: 29874–82
   PubMed Web of Science ®Google Scholar
• Bu G., Maksymovitch E. A., Nerbonne J. M., Schwartz A. L. Expression and function of the low density lipoprotein receptor‐related protein (LRP) in mammalian central neurons. J Biol Chem 1994; 269: 18521–8
   PubMed Web of Science ®Google Scholar
• May P., Rohlmann A., Bock H. H., Zurhove K., Marth J. D., Schomburg E. D., et al. Neuronal LRP1 functionally associates with postsynaptic proteins and is required for normal motor function in mice. Mol Cell Biol 2004; 24: 8872–83
   PubMed Web of Science ®Google Scholar
• Olney J. W., Wozniak D. F., Farber N. B. Excitotoxic neurodegeneration in Alzheimer disease. New hypothesis and new therapeutic strategies. Arch Neurol 1997; 54: 1234–40
   PubMedGoogle Scholar
• Olney J. W., Wozniak D. F., Farber N. B. Glumate receptor dysfunction and Alzheimer's disease. Restor Neurol Neurosci 1998; 13: 75–83
   PubMed Web of Science ®Google Scholar
• Tseng W. F., Huang S. S., Huang J. S. LRP‐1/TbetaR‐V mediates TGF‐beta1‐induced growth inhibition in CHO cells. FEBS Lett 2004; 562: 71–8
   PubMed Web of Science ®Google Scholar
• Qiu Z., Strickland D. K., Hyman B. T., Rebeck G. W. alpha 2‐Macroglobulin exposure reduces calcium responses to N‐methyl‐D‐aspartate via low density lipoprotein receptor‐related protein in cultured hippocampal neurons. J Biol Chem 2002; 277: 14458–66
   PubMed Web of Science ®Google Scholar
• Gardai S. J., Xiao Y. Q., Dickinson M., Nick J. A., Voelker D. R., Greene K. E., et al. By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation. Cell 2003; 115: 13–23
   PubMed Web of Science ®Google Scholar
• Patel M., Morrow J., Maxfield F. R., Strickland D. K., Greenberg S., Tabas I. The cytoplasmic domain of the low density lipoprotein (LDL) receptor‐related protein, but not that of the LDL receptor, triggers phagocytosis. J Biol Chem 2003; 278: 44799–807
   PubMed Web of Science ®Google Scholar
• Gardai S. J., McPhillips K. A., Frasch S. C., Janssen W. J., Starefeldt A., Murphy‐Ullrich J. E., et al. Cell‐surface calreticulin initiates clearance of viable or apoptotic cells through trans‐activation of LRP on the phagocyte. Cell 2005; 123: 321–34
   PubMed Web of Science ®Google Scholar
• Quinn K. A., Pye V. J., Dai Y. P., Chesterman C. N., Owensby D. A. Characterization of the soluble form of the low density lipoprotein receptor‐related protein (LRP). Exp Cell Res 1999; 251: 433–41
   PubMed Web of Science ®Google Scholar
• Quinn K. A., Grimsley P. G., Dai Y. P., Tapner M., Chesterman C. N., Owensby D. A. Soluble low density lipoprotein receptor‐related protein (LRP) circulates in human plasma. J Biol Chem 1997; 272: 23946–51
   PubMed Web of Science ®Google Scholar
• von Arnim C. A., Kinoshita A., Peltan I. D., Tangredi M. M., Herl L., Lee B. M., et al. The low density lipoprotein receptor‐related protein (LRP) is a novel beta‐secretase (BACE1) substrate. J Biol Chem 2005; 280: 17777–85
   PubMed Web of Science ®Google Scholar
• Grimsley P. G., Quinn K. A., Chesterman C. N., Owensby D. A. Evolutionary conservation of circulating soluble low density lipoprotein receptor‐related protein‐like (‘LRP‐like’) molecules. Thromb Res 1999; 94: 153–64
   PubMed Web of Science ®Google Scholar
• May P., Reddy Y. K., Herz J. Proteolytic processing of low density lipoprotein receptor‐related protein mediates regulated release of its intracellular domain. J Biol Chem 2002; 277: 18736–43
   PubMed Web of Science ®Google Scholar
• Brown M. S., Ye J., Rawson R. B., Goldstein J. L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 2000; 100: 391–8
   PubMed Web of Science ®Google Scholar
• Ni C. Y., Murphy M. P., Golde T. E., Carpenter G. gamma ‐Secretase cleavage and nuclear localization of ErbB‐4 receptor tyrosine kinase. Science 2001; 294: 2179–81
   PubMed Web of Science ®Google Scholar
• Okamoto I., Kawano Y., Murakami D., Sasayama T., Araki N., Miki T., et al. Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway. J Cell Biol 2001; 155: 755–62
   PubMed Web of Science ®Google Scholar
• Brown M. S., Goldstein J. L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane‐bound transcription factor. Cell 1997; 89: 331–40
   PubMed Web of Science ®Google Scholar
• Haze K., Yoshida H., Yanagi H., Yura T., Mori K. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 1999; 10: 3787–99
   PubMed Web of Science ®Google Scholar
• Niwa M., Sidrauski C., Kaufman R. J., Walter P. A role for presenilin‐1 in nuclear accumulation of Ire1 fragments and induction of the mammalian unfolded protein response. Cell 1999; 99: 691–702
   PubMed Web of Science ®Google Scholar
• Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., et al. A presenilin‐1/gamma‐secretase cleavage releases the E‐cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 2002; 21: 1948–56
   PubMed Web of Science ®Google Scholar
• Li Y., Marzolo M. P., van Kerkhof P., Strous G. J., Bu G. The YXXL motif, but not the two NPXY motifs, serves as the dominant endocytosis signal for low density lipoprotein receptor‐related protein. J Biol Chem 2000; 275: 17187–94
   PubMed Web of Science ®Google Scholar
• Barnes H., Larsen B., Tyers M., van Der Geer P. Tyrosine‐phosphorylated low density lipoprotein receptor‐related protein 1 (Lrp1) associates with the adaptor protein SHC in SRC‐transformed cells. J Biol Chem 2001; 276: 19119–25
   PubMed Web of Science ®Google Scholar
• Gotthardt M., Trommsdorff M., Nevitt M. F., Shelton J., Richardson J. A., Stockinger W., et al. Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction. J Biol Chem 2000; 275: 25616–24
   PubMed Web of Science ®Google Scholar
• Su H. P., Nakada‐Tsukui K., Tosello‐Trampont A. C., Li Y., Bu G., Henson P. M., et al. Interaction of CED‐6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED‐1 and CD91/low density lipoprotein receptor‐related protein (LRP). J Biol Chem 2002; 277: 11772–9
   PubMed Web of Science ®Google Scholar
• Trommsdorff M., Borg J. P., Margolis B., Herz J. Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein. J Biol Chem 1998; 273: 33556–60
   PubMed Web of Science ®Google Scholar
• Chang Y., Tesco G., Jeong W. J., Lindsley L., Eckman E. A., Eckman C. B., et al. Generation of the beta‐amyloid peptide and the amyloid precursor protein C‐terminal fragment gamma are potentiated by FE65L1. J Biol Chem 2003; 278: 51100–7
   PubMed Web of Science ®Google Scholar
• Kinoshita A., Shah T., Tangredi M. M., Strickland D. K., Hyman B. T. The intracellular domain of the low density lipoprotein receptor‐related protein modulates transactivation mediated by amyloid precursor protein and Fe65. J Biol Chem 2003; 278: 41182–8
   PubMed Web of Science ®Google Scholar
• Baek S. H., Ohgi K. A., Rose D. W., Koo E. H., Glass C. K., Rosenfeld M. G. Exchange of N‐CoR corepressor and Tip60 coactivator complexes links gene expression by NF‐kappaB and beta‐amyloid precursor protein. Cell 2002; 110: 55–67
   PubMed Web of Science ®Google Scholar
• Cao X., Sudhof T. C. A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 2001; 293: 115–20
   PubMed Web of Science ®Google Scholar
• Roebroek A. J., Reekmans S., Lauwers A., Feyaerts N., Smeijers L., Hartmann D. Mutant Lrp1 knock‐in mice generated by recombinase‐mediated cassette exchange reveal differential importance of the NPXY motifs in the intracellular domain of LRP1 for normal fetal development. Mol Cell Biol 2006; 26: 605–16
   PubMed Web of Science ®Google Scholar
• Kerjaschki D., Farquhar M. G. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci U S A 1982; 79: 5557–61
   PubMed Web of Science ®Google Scholar
• Saito A., Pietromonaco S., Loo A. K., Farquhar M. G. Complete cloning and sequencing of rat gp330/‘megalin’, a distinctive member of the low density lipoprotein receptor gene family. Proc Natl Acad Sci U S A 1994; 91: 9725–9
   PubMed Web of Science ®Google Scholar
• Christensen E. I., Nielsen S., Moestrup S. K., Borre C., Maunsbach A. B., de Heer E., et al. Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules. Eur J Cell Biol 1995; 66: 349–64
   PubMed Web of Science ®Google Scholar
• Muller D., Nykjaer A., Willnow T. E. From holoprosencephaly to osteopathology: role of multifunctional endocytic receptors in absorptive epithelia. Ann Med 2003; 35: 290–9
   PubMed Web of Science ®Google Scholar
• May P., Herz J., Bock H. H. Molecular mechanisms of lipoprotein receptor signalling. Cell Mol Life Sci 2005; 62: 2325–38
   PubMed Web of Science ®Google Scholar
• Nykjaer A., Dragun D., Walther D., Vorum H., Jacobsen C., Herz J., et al. An endocytic pathway essential for renal uptake and activation of the steroid 25‐(OH) vitamin D3. Cell 1999; 96: 507–15
   PubMed Web of Science ®Google Scholar
• Farese R. V., Jr., Herz J. Cholesterol metabolism and embryogenesis. Trends Genet 1998; 14: 115–20
   PubMed Web of Science ®Google Scholar
• Christensen E. I., Moskaug J. O., Vorum H., Jacobsen C., Gundersen T. E., Nykjaer A., et al. Evidence for an essential role of megalin in transepithelial transport of retinol. J Am Soc Nephrol 1999; 10: 685–95
   PubMed Web of Science ®Google Scholar
• Moestrup S. K., Birn H., Fischer P. B., Petersen C. M., Verroust P. J., Sim R. B., et al. Megalin‐mediated endocytosis of transcobalamin‐vitamin‐B12 complexes suggests a role of the receptor in vitamin‐B12 homeostasis. Proc Natl Acad Sci U S A 1996; 93: 8612–7
   PubMed Web of Science ®Google Scholar
• Leheste J. R., Melsen F., Wellner M., Jansen P., Schlichting U., Renner‐Muller I., et al. Hypocalcemia and osteopathy in mice with kidney‐specific megalin gene defect. FASEB J 2003; 17: 247–9
   PubMed Web of Science ®Google Scholar
• Hammes A., Andreassen T. K., Spoelgen R., Raila J., Hubner N., Schulz H., et al. Role of endocytosis in cellular uptake of sex steroids. Cell 2005; 122: 751–62
   PubMed Web of Science ®Google Scholar
• Zou Z., Chung B., Nguyen T., Mentone S., Thomson B., Biemesderfer D. Linking receptor‐mediated endocytosis and cell signaling: evidence for regulated intramembrane proteolysis of megalin in proximal tubule. J Biol Chem 2004; 279: 34302–10
   PubMed Web of Science ®Google Scholar
• Petersen H. H., Hilpert J., Militz D., Zandler V., Jacobsen C., Roebroek A. J., et al. Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat‐containing adaptor molecule. J Cell Sci 2003; 116: 453–61
   PubMed Web of Science ®Google Scholar
• Nakayama M., Nakajima D., Nagase T., Nomura N., Seki N., Ohara O. Identification of high‐molecular‐weight proteins with multiple EGF‐like motifs by motif‐trap screening. Genomics 1998; 51: 27–34
   PubMed Web of Science ®Google Scholar
• Chen W. J., Goldstein J. L., Brown M. S. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit‐mediated internalization of the low density lipoprotein receptor. J Biol Chem 1990; 265: 3116–23
   PubMed Web of Science ®Google Scholar
• Nykjaer A., Willnow T. E. The low‐density lipoprotein receptor gene family: a cellular Swiss army knife?. Trends Cell Biol 2002; 12: 273–80
   PubMed Web of Science ®Google Scholar
• Mao B., Wu W., Li Y., Hoppe D., Stannek P., Glinka A., et al. LDL‐receptor‐related protein 6 is a receptor for Dickkopf proteins. Nature 2001; 411: 321–5
   PubMed Web of Science ®Google Scholar
• Mao J., Wang J., Liu B., Pan W., Farr G. H 3rd., Flynn C., et al. Low‐density lipoprotein receptor‐related protein‐5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 2001; 7: 801–9
   PubMed Web of Science ®Google Scholar
• Yamaguchi Y. L., Tanaka S. S., Kasa M., Yasuda K., Tam P. P., Matsui Y. Expression of low density lipoprotein receptor‐related protein 4 (Lrp4) gene in the mouse germ cells. Gene Expr Patterns 2006; 6: 607–12
   PubMed Web of Science ®Google Scholar
• Johnson E. B., Hammer R. E., Herz J. Abnormal development of the apical ectodermal ridge and polysyndactyly in Megf7‐deficient mice. Hum Mol Genet 2005; 14: 3523–38
   PubMed Web of Science ®Google Scholar
• Capdevila J., Izpisua Belmonte J. C. Patterning mechanisms controlling vertebrate limb development. Annu Rev Cell Dev Biol 2001; 17: 87–132
   PubMed Web of Science ®Google Scholar
• Simon‐Chazottes D., Tutois S., Kuehn M., Evans M., Bourgade F., Cook S., et al. Mutations in the gene encoding the low‐density lipoprotein receptor LRP4 cause abnormal limb development in the mouse. Genomics 2006; 87: 673–7
   PubMed Web of Science ®Google Scholar
• Duchesne A., Gautier M., Chadi S., Grohs C., Floriot S., Gallard Y., et al. Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle. Genomics 2006; 88: 610–21
   PubMed Web of Science ®Google Scholar
• Tian Q. B., Suzuki T., Yamauchi T., Sakagami H., Yoshimura Y., Miyazawa S., et al. Interaction of LDL receptor‐related protein 4 (LRP4) with postsynaptic scaffold proteins via its C‐terminal PDZ domain‐binding motif, and its regulation by Ca/calmodulin‐dependent protein kinase II. Eur J Neurosci 2006; 23: 2864–76
   PubMed Web of Science ®Google Scholar
• Sousa M. M., Norden A. G., Jacobsen C., Willnow T. E., Christensen E. I., Thakker R. V., et al. Evidence for the role of megalin in renal uptake of transthyretin. J Biol Chem 2000; 275: 38176–81
   PubMed Web of Science ®Google Scholar
• Stefansson S., Chappell D. A., Argraves K. M., Strickland D. K., Argraves W. S. Glycoprotein 330/low density lipoprotein receptor‐related protein‐2 mediates endocytosis of low density lipoproteins via interaction with apolipoprotein B100. J Biol Chem 1995; 270: 19417–21
   PubMed Web of Science ®Google Scholar
• Willnow T. E., Goldstein J. L., Orth K., Brown M. S., Herz J. Low density lipoprotein receptor‐related protein and gp330 bind similar ligands, including plasminogen activator‐inhibitor complexes and lactoferrin, an inhibitor of chylomicron remnant clearance. J Biol Chem 1992; 267: 26172–80
   PubMed Web of Science ®Google Scholar
• Niemeier A., Willnow T., Dieplinger H., Jacobsen C., Meyer N., Hilpert J., et al. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro. Arterioscler Thromb Vasc Biol 1999; 19: 552–61
   PubMed Web of Science ®Google Scholar
• Moestrup S. K., Schousboe I., Jacobsen C., Leheste J. R., Christensen E. I., Willnow T. E. Beta2‐glycoprotein‐I (apolipoprotein H) and beta2‐glycoprotein‐I‐phospholipid complex harbor a recognition site for the endocytic receptor megalin. J Clin Invest 1998; 102: 902–9
   PubMed Web of Science ®Google Scholar
• Kounnas M. Z., Loukinova E. B., Stefansson S., Harmony J. A., Brewer B. H., strickland D. K., et al. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J Biol Chem 1995; 270: 13070–5
   PubMed Web of Science ®Google Scholar