Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpa 2MR, and the receptor-associated protein (RAP)G Zheng, DR Bachinsky, I Stamenkovic, DK Strickland, D Brown, G Andres and RT McCluskey Department of Pathology, Massachusetts General Hospital, Boston. We investigated immunohistochemically the distribution in rats of the homologous proteins gp330 and the LDL receptor-related protein (LRP/alpha 2MR), and a receptor-associated protein (RAP), and the sites to which soluble exogenous RAP binds. We found gp330 in a restricted group of epithelial cells, including renal proximal tubule cells, podocytes, Type II pneumocytes, cells of the parathyroid, thyroid, epididymis, lining of the uterus, ependyma, retina, ciliary body, yolk sac, and placenta. In these cells gp330 was detected mainly at the cell surface, except for parathyroid and retinal epithelial cells, where diffuse cell staining was found. LRP/alpha 2MR was widely distributed in interstitial cells, notably in fibroblasts and macrophages, and was also present in a selected group of epithelial or specialized cells, including hepatocytes, adrenal cortical cells, follicular cells of the ovary, cells of the choroid plexus, ciliary body, mesangial cells, and some neurons. In certain cells, notably hepatocytes and adrenal cortical cells, LRP/alpha 2MR was detected mainly on the surface, but in others, including macrophages, fibroblasts, and epithelial cells of the choroid plexus and ciliary body, staining throughout the cell was seen. The only cells that clearly expressed both LRP/alpha 2MR and gp330 were retinal and ciliary epithelial cells. RAP was found in intracellular vesicles in all cells that expressed gp330 or LRP/alpha 2MR. RAP was not definitely detected on the cell surface. Binding sites for RAP were found on the surface of those cells with surface gp330 or LRP, and also throughout the cytoplasm in cells with diffuse cellular LRP/alpha 2MR or gp330. Because of their different locations, we conclude that gp330 and LRP/alpha 2MR serve distinct functions in vivo, despite similarities in ligand-binding properties observed in vitro. Since RAP is found largely within cells, its major physiological function may be concerned with intracellular assembly or trafficking of the receptors to which it binds.
Volume 42,
Issue 4,
pp. 531-542,
04/01/1994
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G. E. Olson, V. P. Winfrey, K. E. Hill, and R. F. Burk Megalin Mediates Selenoprotein P Uptake by Kidney Proximal Tubule Epithelial Cells J. Biol. Chem., March 14, 2008; 283(11): 6854 - 6860. [Abstract] [Full Text] [PDF] |
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A. N.-S. Mak, Y.-T. Wong, Y.-J. An, S.-S. Cha, K.-H. Sze, S. W.-N. Au, K.-B. Wong, and P.-C. Shaw Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site Nucleic Acids Res., September 25, 2007; 35(18): 6259 - 6267. [Abstract] [Full Text] [PDF] |
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S. Kurumada, A. Onishi, H. Imai, K. Ishii, T. Kobayashi, and S. B. Sato Stage-Specific Association of Apolipoprotein A-I and E in Developing Mouse Retina Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1815 - 1823. [Abstract] [Full Text] [PDF] |
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S. Azhar, S. Medicherla, W.-J. Shen, Y. Fujioka, L. G. Fong, E. Reaven, and A. D. Cooper LDL and cAMP cooperate to regulate the functional expression of the LRP in rat ovarian granulosa cells J. Lipid Res., November 1, 2006; 47(11): 2538 - 2550. [Abstract] [Full Text] [PDF] |
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A. Tramontano, T. Knight, D. Vizzuso, and S. P. Makker Nested N-Terminal Megalin Fragments Induce High-Titer Autoantibody and Attenuated Heymann Nephritis J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1979 - 1985. [Abstract] [Full Text] [PDF] |
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A. Matsubara, T. Nakazawa, D. Husain, E. Iliaki, E. Connolly, N. A. Michaud, E. S. Gragoudas, and J. W. Miller Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2498 - 2507. [Abstract] [Full Text] [PDF] |
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S. Lisi, R. Botta, A. Pinchera, A. B. Collins, S. Refetoff, P. Arvan, G. Bu, L. Grasso, V. Marshansky, S. Bechoua, et al. Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1160 - C1167. [Abstract] [Full Text] [PDF] |
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K. Faber, V. Hvidberg, S. K. Moestrup, B. Dahlback, and L. B. Nielsen Megalin Is a Receptor for Apolipoprotein M, and Kidney-Specific Megalin-Deficiency Confers Urinary Excretion of Apolipoprotein M Mol. Endocrinol., January 1, 2006; 20(1): 212 - 218. [Abstract] [Full Text] [PDF] |
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L. A Woollett Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1155 - 1161. [Abstract] [Full Text] [PDF] |
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B. C. Lin and T. S. Scanlan Few Things in Life are "Free": Cellular Uptake of Steroid Hormones by an Active Transport Mechanism Mol. Interv., December 1, 2005; 5(6): 338 - 340. [Abstract] [Full Text] [PDF] |
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W. J. Cain, J. S. Millar, A. S. Himebauch, U. J. F. Tietge, C. Maugeais, D. Usher, and D. J. Rader Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a] J. Lipid Res., December 1, 2005; 46(12): 2681 - 2691. [Abstract] [Full Text] [PDF] |
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S. Yoshida and Y. Wada Transfer of maternal cholesterol to embryo and fetus in pregnant mice J. Lipid Res., October 1, 2005; 46(10): 2168 - 2174. [Abstract] [Full Text] [PDF] |
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R. Spoelgen, A. Hammes, U. Anzenberger, D. Zechner, O. M. Andersen, B. Jerchow, and T. E. Willnow LRP2/megalin is required for patterning of the ventral telencephalon Development, January 15, 2005; 132(2): 405 - 414. [Abstract] [Full Text] [PDF] |
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B. Erranz, J. F. Miquel, W. S. Argraves, J. L. Barth, F. Pimentel, and M.-P. Marzolo Megalin and cubilin expression in gallbladder epithelium and regulation by bile acids J. Lipid Res., December 1, 2004; 45(12): 2185 - 2198. [Abstract] [Full Text] [PDF] |
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W. Pan, A. J. Kastin, T. C. Zankel, P. van Kerkhof, T. Terasaki, and G. Bu Efficient transfer of receptor-associated protein (RAP) across the blood-brain barrier J. Cell Sci., October 1, 2004; 117(21): 5071 - 5078. [Abstract] [Full Text] [PDF] |
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A. Tramontano and S. P. Makker Conformation and Glycosylation of a Megalin Fragment Correlate with Nephritogenicity in Heymann Nephritis J. Immunol., February 15, 2004; 172(4): 2367 - 2373. [Abstract] [Full Text] [PDF] |
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M. B. Gilardoni, D. G. Ceschin, M. M. Sahores, M. Oviedo, R. C. Gehrau, and G. A. Chiabrando Decreased Expression of the Low-density Lipoprotein Receptor-related Protein-1 (LRP-1) in Rats with Prostate Cancer J. Histochem. Cytochem., December 1, 2003; 51(12): 1575 - 1580. [Abstract] [Full Text] [PDF] |
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M. Nagai, T. Meerloo, T. Takeda, and M. G. Farquhar The Adaptor Protein ARH Escorts Megalin to and through Endosomes Mol. Biol. Cell, December 1, 2003; 14(12): 4984 - 4996. [Abstract] [Full Text] [PDF] |
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A. Saito, J. J. Kazama, N. Iino, K. Cho, N. Sato, H. Yamazaki, Y. Oyama, T. Takeda, R. A. Orlando, F. Shimizu, et al. Bioengineered Implantation of Megalin-Expressing Cells: A Potential Intracorporeal Therapeutic Model for Uremic Toxin Protein Clearance in Renal Failure J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2025 - 2032. [Abstract] [Full Text] [PDF] |
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T. Takeda, H. Yamazaki, and M. G. Farquhar Identification of an apical sorting determinant in the cytoplasmic tail of megalin Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1105 - C1113. [Abstract] [Full Text] [PDF] |
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I. Kolleck, P. Sinha, and B. Rustow Vitamin E as an Antioxidant of the Lung: Mechanisms of Vitamin E Delivery to Alveolar Type II Cells Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S62 - 66. [Abstract] [Full Text] [PDF] |
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C. R. Harlow, L. Davidson, K. H. Burns, C. Yan, M. M. Matzuk, and S. G. Hillier FSH and TGF-{beta} Superfamily Members Regulate Granulosa Cell Connective Tissue Growth Factor Gene Expression in Vitro and in Vivo Endocrinology, September 1, 2002; 143(9): 3316 - 3325. [Abstract] [Full Text] [PDF] |
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I. Kolleck, H. Wissel, F. Guthmann, M. Schlame, P. Sinha, and B. Rustow HDL-Holoparticle Uptake by Alveolar Type II Cells . Effect of Vitamin E Status Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 57 - 63. [Abstract] [Full Text] [PDF] |
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U. Segersten, P. Correa, M. Hewison, P. Hellman, H. Dralle, T. Carling, G. Akerstrom, and G. Westin 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase Expression in Normal and Pathological Parathyroid Glands J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2967 - 2972. [Abstract] [Full Text] [PDF] |
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Z. Qiu, D. K. Strickland, B. T. Hyman, and G. W. Rebeck 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., April 19, 2002; 277(17): 14458 - 14466. [Abstract] [Full Text] [PDF] |
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H. Birn, T. E. Willnow, R. Nielsen, A. G. W. Norden, C. Bonsch, S. K. Moestrup, E. Nexo, and E. I. Christensen Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B12 Am J Physiol Renal Physiol, March 1, 2002; 282(3): F408 - F416. [Abstract] [Full Text] [PDF] |
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M. Marino, L. Chiovato, S. Lisi, A. Pinchera, and R. T. McCluskey Binding of the Low Density Lipoprotein Receptor-Associated Protein (RAP) to Thyroglobulin (Tg): Putative Role of RAP in the Tg Secretory Pathway Mol. Endocrinol., October 1, 2001; 15(10): 1829 - 1837. [Abstract] [Full Text] [PDF] |
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J. Nagai, H. Tanaka, N. Nakanishi, T. Murakami, and M. Takano Role of megalin in renal handling of aminoglycosides Am J Physiol Renal Physiol, August 1, 2001; 281(2): F337 - F344. [Abstract] [Full Text] [PDF] |
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J. A. McConihay, P. S. Horn, and L. A. Woollett Effect of maternal hypercholesterolemia on fetal sterol metabolism in the Golden Syrian hamster J. Lipid Res., July 1, 2001; 42(7): 1111 - 1119. [Abstract] [Full Text] [PDF] |
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M. MARINO, D. ANDREWS, D. BROWN, and R. T. McCLUSKEY Transcytosis of Retinol-Binding Protein across Renal Proximal Tubule Cells after Megalin (gp 330)-Mediated Endocytosis J. Am. Soc. Nephrol., April 1, 2001; 12(4): 637 - 648. [Abstract] [Full Text] [PDF] |
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K. M. PATRIE, A. J. DRESCHER, M. GOYAL, R. C. WIGGINS, and B. MARGOLIS The Membrane-Associated Guanylate Kinase Protein MAGI-1 Binds Megalin and Is Present in Glomerular Podocytes J. Am. Soc. Nephrol., April 1, 2001; 12(4): 667 - 677. [Abstract] [Full Text] [PDF] |
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E. I. Christensen and H. Birn Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule Am J Physiol Renal Physiol, April 1, 2001; 280(4): F562 - F573. [Abstract] [Full Text] [PDF] |
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L. Obermoeller-McCormick, Y Li, H Osaka, D. FitzGerald, A. Schwartz, and G Bu Dissection of receptor folding and ligand-binding property with functional minireceptors of LDL receptor-related protein J. Cell Sci., January 3, 2001; 114(5): 899 - 908. [Abstract] [PDF] |
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Y. Hashimoto, H. Jiang, T. Niikura, Y. Ito, A. Hagiwara, K. Umezawa, Y. Abe, Y. Murayama, and I. Nishimoto Neuronal Apoptosis by Apolipoprotein E4 through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases J. Neurosci., November 15, 2000; 20(22): 8401 - 8409. [Abstract] [Full Text] [PDF] |
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M. Marino and R. T. McCluskey Role of thyroglobulin endocytic pathways in the control of thyroid hormone release Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1295 - C1306. [Abstract] [Full Text] [PDF] |
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M. Marinò, L. Chiovato, N. Mitsiades, F. Latrofa, D. Andrews, S. Tseleni-Balafouta, A. B. Collins, A. Pinchera, and R. T. McCluskey Circulating Thyroglobulin Transcytosed by Thyroid Cells Is Complexed with Secretory Components of Its Endocytic Receptor Megalin J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3458 - 3467. [Abstract] [Full Text] |
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M. Marino, G. Zheng, L. Chiovato, A. Pinchera, D. Brown, D. Andrews, and R. T. McCluskey Role of Megalin (gp330) in Transcytosis of Thyroglobulin by Thyroid Cells. A NOVEL FUNCTION IN THE CONTROL OF THYROID HORMONE RELEASE J. Biol. Chem., March 15, 2000; 275(10): 7125 - 7137. [Abstract] [Full Text] [PDF] |
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J. A. McConihay, A. M. Honkomp, N. A. Granholm, and L. A. Woollett Maternal high density lipoproteins affect fetal mass and extra-embryonic fetal tissue sterol metabolism in the mouse J. Lipid Res., March 1, 2000; 41(3): 424 - 432. [Abstract] [Full Text] |
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W. Morelle, S. M. Haslam, M. Ziak, J. Roth, H. R. Morris, and A. Dell Characterization of the N-linked oligosaccharides of megalin (gp330) from rat kidney Glycobiology, March 1, 2000; 10(3): 295 - 304. [Abstract] [Full Text] [PDF] |
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M. Marino, J. A. Friedlander, R. T. McCluskey, and D. Andrews Identification of a Heparin-binding Region of Rat Thyroglobulin Involved in Megalin Binding J. Biol. Chem., October 22, 1999; 274(43): 30377 - 30386. [Abstract] [Full Text] [PDF] |
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O. Y. Barmina, H. W. Walling, G. J. Fiacco, J. M. P. Freije, C. Lopez-Otin, J. J. Jeffrey, and N. C. Partridge Collagenase-3 Binds to a Specific Receptor and Requires the Low Density Lipoprotein Receptor-related Protein for Internalization J. Biol. Chem., October 15, 1999; 274(42): 30087 - 30093. [Abstract] [Full Text] [PDF] |
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E. I. CHRISTENSEN and T. E. WILLNOW Essential Role of Megalin in Renal Proximal Tubule for Vitamin Homeostasis J. Am. Soc. Nephrol., October 1, 1999; 10(10): 2224 - 2236. [Full Text] |
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M. Marinò, L. Chiovato, J. A. Friedlander, F. Latrofa, A. Pinchera, and R. T. McCluskey Serum Antibodies against Megalin (GP330) in Patients with Autoimmune Thyroiditis J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2468 - 2474. [Abstract] [Full Text] |
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M.-P. Mingeot-Leclercq and P. M. Tulkens Aminoglycosides: Nephrotoxicity Antimicrob. Agents Chemother., May 1, 1999; 43(5): 1003 - 1012. [Full Text] |
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M. Marino, G. Zheng, and R. T. McCluskey Megalin (gp330) Is an Endocytic Receptor for Thyroglobulin on Cultured Fisher Rat Thyroid Cells J. Biol. Chem., April 30, 1999; 274(18): 12898 - 12904. [Abstract] [Full Text] [PDF] |
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A. Niemeier, T. Willnow, H. Dieplinger, C. Jacobsen, N. Meyer, J. Hilpert, and U. Beisiegel Identification of Megalin/gp330 as a Receptor for Lipoprotein(a) In Vitro Arterioscler. Thromb. Vasc. Biol., March 1, 1999; 19(3): 552 - 561. [Abstract] [Full Text] [PDF] |
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S. Ranganathan, C. Knaak, C. R. Morales, and W. S. Argraves Identification of Low Density Lipoprotein Receptor-related Protein-2/megalin as an Endocytic Receptor for Seminal Vesicle Secretory Protein II J. Biol. Chem., February 26, 1999; 274(9): 5557 - 5563. [Abstract] [Full Text] [PDF] |
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A Simon, A Romert, A. Gustafson, J. McCaffery, and U Eriksson Intracellular localization and membrane topology of 11-cis retinol dehydrogenase in the retinal pigment epithelium suggest a compartmentalized synthesis of 11-cis retinaldehyde J. Cell Sci., January 2, 1999; 112(4): 549 - 558. [Abstract] [PDF] |
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G. Zhang, L. K. Curtiss, R. L. Wade, and C. A. Dyer An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17{alpha}-hydroxylase, C17–20 lyase J. Lipid Res., December 1, 1998; 39(12): 2406 - 2414. [Abstract] [Full Text] |
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W. Stockinger, E. Hengstschlager-Ottnad, S. Novak, A. Matus, M. Huttinger, J. Bauer, H. Lassmann, W. J. Schneider, and J. Nimpf The Low Density Lipoprotein Receptor Gene Family. DIFFERENTIAL EXPRESSION OF TWO alpha 2-MACROGLOBULIN RECEPTORS IN THE BRAIN J. Biol. Chem., November 27, 1998; 273(48): 32213 - 32221. [Abstract] [Full Text] [PDF] |
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A. K. Hatzopoulos, A. Rigotti, R. D. Rosenberg, and M. Krieger Temporal and spatial pattern of expression of the HDL receptor SR-BI during murine embryogenesis J. Lipid Res., March 1, 1998; 39(3): 495 - 508. [Abstract] [Full Text] |
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K. L. Wyne and L. A. Woollett Transport of maternal LDL and HDL to the fetal membranes and placenta of the Golden Syrian hamster is mediated by receptor-dependent and receptor-independent processes J. Lipid Res., March 1, 1998; 39(3): 518 - 530. [Abstract] [Full Text] |
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R. B. DeMattos, L. K. Curtiss, and D. L. Williams A Minimally Lipidated Form of Cell-derived Apolipoprotein E Exhibits Isoform-specific Stimulation of Neurite Outgrowth in the Absence of Exogenous Lipids or Lipoproteins J. Biol. Chem., February 13, 1998; 273(7): 4206 - 4212. [Abstract] [Full Text] [PDF] |
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J. Jordan, M. F. Galindo, R. J. Miller, C. A. Reardon, G. S. Getz, and M. J. LaDu Isoform-Specific Effect of Apolipoprotein E on Cell Survival and beta -Amyloid-Induced Toxicity in Rat Hippocampal Pyramidal Neuronal Cultures J. Neurosci., January 1, 1998; 18(1): 195 - 204. [Abstract] [Full Text] [PDF] |
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M. Tolar, M. A. Marques, J. A. K. Harmony, and K. A. Crutcher Neurotoxicity of the 22 kDa Thrombin-Cleavage Fragment of Apolipoprotein E and Related Synthetic Peptides Is Receptor-Mediated J. Neurosci., August 1, 1997; 17(15): 5678 - 5686. [Abstract] [Full Text] [PDF] |
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S. M. Hammad, S. Ranganathan, E. Loukinova, W. O. Twal, and W. S. Argraves Interaction of Apolipoprotein J-Amyloid beta -Peptide Complex with Low Density Lipoprotein Receptor-related Protein-2/Megalin. A MECHANISM TO PREVENT PATHOLOGICAL ACCUMULATION OF AMYLOID beta -PEPTIDE J. Biol. Chem., July 25, 1997; 272(30): 18644 - 18649. [Abstract] [Full Text] [PDF] |
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R. A. Orlando, M. Exner, R.-P. Czekay, H. Yamazaki, A. Saito, R. Ullrich, D. Kerjaschki, and M. G. Farquhar Identification of the second cluster of ligand-binding repeats in megalin as a site for receptor-ligand interactions PNAS, March 18, 1997; 94(6): 2368 - 2373. [Abstract] [Full Text] [PDF] |
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I. Mikhailenko, D. Krylov, K. M. Argraves, D. D. Roberts, G. Liau, and D. K. Strickland Cellular Internalization and Degradation of Thrombospondin-1 Is Mediated by the Amino-terminal Heparin Binding Domain (HBD). HIGH AFFINITY INTERACTION OF DIMERIC HBD WITH THE LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN J. Biol. Chem., March 7, 1997; 272(10): 6784 - 6791. [Abstract] |