Role of megalin and cubilin in renal physiology and pathophysiology (original) (raw)

References

• Aminoff M, Carter JE, Chadwick RB, Johnson C, Grasbeck R, Abdelaal MA, Broch H, Jenner LB, Verroust PJ, Moestrup SK, de la Chapelle A, Krahe R (1999) Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat Genet 21:309–313
  Article PubMed CAS Google Scholar
• Bachinsky DR, Zheng G, Niles JL, McLaughlin M, Abbate M, Andres G, Brown D, McCluskey RT (1993) Detection of two forms of GP330. Their role in Heymann nephritis. Am J Pathol 143:598–611
  PubMed CAS Google Scholar
• Batuman V, Verroust PJ, Navar GL, Kaysen JH, Goda FO, Campbell WC, Simon E, Pontillon F, Lyles M, Bruno J, Hammond TG (1998) Myeloma light chains are ligands for cubilin (gp280). Am J Physiol Renal Physiol 275:F246–F254
  CAS Google Scholar
• Biemesderfer D, Nagy T, DeGray B, Aronson PS (1999) Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule. J Biol Chem 274:17518–17524
  Article PubMed CAS Google Scholar
• Birn H, Fyfe JC, Jacobsen C, Mounier F, Verroust PJ, Orskov H, Willnow TE, Moestrup SK, Christensen EI (2000a) Cubilin is an albumin binding protein important for renal tubular albumin reabsorption. J Clin Invest 105:1353–1361
  Article PubMed CAS Google Scholar
• Birn H, Leboulleux M, Moestrup SK, Ronco PM, Aucouturier P, Christensen EI (2003) Megalin, cubilin and immunoglobulin light chains: receptor-mediated uptake of light chains in kidney proximal tubule. In: Touchard G, Aucouturier P, Hermine O, Ronco PM (eds) Monoclonal Gammopathies and the Kidney. Kluwer, The Netherlands, pp 37–48
  Google Scholar
• Birn H, Verroust PJ, Nexø E, Hager H, Jacobsen C, Christensen EI, Moestrup SK (1997) Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein. J Biol Chem 272:26497–26504
  Article PubMed CAS Google Scholar
• Birn H, Vorum H, Verroust PJ, Moestrup SK, Christensen EI (2000b) Receptor-associated protein is important for normal processing of megalin in kidney proximal tubules. J Am Soc Nephrol 11:191–202
  PubMed CAS Google Scholar
• Birn H, Zhai X, Holm J, Hansen SI, Jacobsen C, Christensen EI, Moestrup SK (2005) Megalin binds and mediates cellular internalization of folate binding protein. FEBS J 272:4423–4430
  Article PubMed CAS Google Scholar
• Bork P, Beckmann G (1993) The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol 231:539–545
  Article PubMed CAS Google Scholar
• Branton M, Schiffmann R, Kopp JB (2002) Natural history and treatment of renal involvement in Fabry disease. J Am Soc Nephrol 13(Suppl 2):S139–S143
  PubMed Google Scholar
• Bu G, Geuze HJ, Strous GJ, Schwartz AL (1995) 39 kDa receptor-associated protein is an ER resident protein and molecular chaperone for LDL receptor-related protein. EMBO J 14:2269–2280
  PubMed CAS Google Scholar
• Bu G, Rennke S (1996) Receptor-associated protein is a folding chaperone for low density lipoprotein receptor-related protein. J Biol Chem 271:22218–22224
  Article PubMed CAS Google Scholar
• Burmeister R, Boe IM, Nykjaer A, Jacobsen C, Moestrup SK, Verroust P, Christensen EI, Lund J, Willnow TE (2001) A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney. J Biol Chem 276:13295–13301
  Article PubMed CAS Google Scholar
• Chan WL, Shaw PC, Tam SC, Jacobsen C, Gliemann J, Nielsen MS (2000) Trichosanthin interacts with and enters cells via LDL receptor family members. Biochem Biophys Res Commun 270(2):453–457
  Article PubMed CAS Google Scholar
• Chatelet F, Brianti E, Ronco P, Roland J, Verroust P (1986) Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. I. Renal distribution. Am J Pathol 122:500–511
  PubMed CAS Google Scholar
• Christensen EI (1982) Rapid membrane recycling in renal proximal tubule cells. Eur J Cell Biol 29:43–49
  PubMed CAS Google Scholar
• Christensen EI, Birn H (2002) Megalin and cubilin: multifunctional endocytic receptors. Nat Rev Mol Cell Biol 3:256–266
  PubMed CAS Google Scholar
• Christensen EI, Birn H (2001) Megalin and cubilin: synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol 280:F562–F573
  PubMed CAS Google Scholar
• Christensen EI, Birn H, Verroust P, Moestrup SK (1998) Membrane receptors for endocytosis in the renal proximal tubule. Int Rev Cytol 180:237–284
  Article PubMed CAS Google Scholar
• Christensen EI, Carone FA, Rennke HG (1981) Effect of molecular charge on endocytic uptake of ferritin in renal proximal tubule cells. Lab Invest 44:351–358
  PubMed CAS Google Scholar
• Christensen EI, Devuyst O, Dom G, Nielsen R, Van Der Smissen P, Verroust P, Leruth M, Guggino WB, Courtoy PJ (2003) Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci USA 100:8472–8477
  Article PubMed CAS Google Scholar
• Christensen EI, Gliemann J, Moestrup SK (1992) Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein. J Histochem Cytochem 40:1481–1490
  Article PubMed CAS Google Scholar
• Christensen EI, Moskaug JO, Vorum H, Jacobsen C, Gundersen TE, Nykjaer A, Blomhoff R, Willnow TE, Moestrup SK (1999) Evidence for an essential role of megalin in transepithelial transport of retinol. J Am Soc Nephrol 10:685–695
  PubMed CAS Google Scholar
• Christensen EI, Nielsen S, Moestrup SK, Borre C, Maunsbach AB, de Heer E, Ronco P, Hammond TG, Verroust P (1995) Segmental distribution of the endocytosis receptor gp330 in renal proximal tubules. Eur J Cell Biol 66:349–364
  PubMed CAS Google Scholar
• Coudroy G, Gburek J, Kozyraki R, Madsen M, Trugnan G, Moestrup SK, Verroust PJ, Maurice M (2005) Contribution of cubilin and amnionless to processing and membrane targeting of cubilin-amnionless complex. J Am Soc Nephrol 16:2330–2337
  Article PubMed CAS Google Scholar
• Cui S, Verroust PJ, Moestrup SK, Christensen EI (1996) Megalin/gp330 mediates uptake of albumin in renal proximal tubule. Am J Physiol 271:F900–F907
  PubMed CAS Google Scholar
• Davis CG, Goldstein JL, Sudhof TC, Anderson RG, Russell DW, Brown MS (1987) Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. Nature 326:760–765
  Article PubMed CAS Google Scholar
• Devuyst O, Christie PT, Courtoy PJ, Beauwens R, Thakker RV (1999) Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease. Hum Mol Genet 8:247–257
  Article PubMed CAS Google Scholar
• Donaldson JG, Honda A (2005) Localization and function of Arf family GTPases. Biochem Soc Trans 33:639–642
  Article PubMed CAS Google Scholar
• Dressman MA, Olivos-Glander IM, Nussbaum RL, Suchy SF (2000) Ocrl1, a PtdIns(4,5)P(2) 5-phosphatase, is localized to the trans-Golgi network of fibroblasts and epithelial cells. J Histochem Cytochem 48:179–190
  Article PubMed CAS Google Scholar
• Faber K, Hvidberg V, Moestrup SK, Dahlback B, Nielsen LB (2006) Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M. Mol Endocrinol 20:212–218
  Article PubMed CAS Google Scholar
• Fyfe JC, Madsen M, Hojrup P, Christensen EI, Tanner SM, de la Chapelle A, He Q, Moestrup SK (2004) The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood 103:1573–1579
  Article PubMed CAS Google Scholar
• Fyfe JC, Ramanujam KS, Ramaswamy K, Patterson DF, Seetharam B (1991) Defective brush-border expression of intrinsic factor-cobalamin receptor in canine inherited intestinal cobalamin malabsorption. J Biol Chem 266:4489–4494
  PubMed CAS Google Scholar
• Gburek J, Birn H, Verroust PJ, Goj B, Jacobsen C, Moestrup SK, Willnow TE, Christensen EI (2003) Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin. Am J Physiol Renal Physiol 285:F451–F458
  PubMed Google Scholar
• Gburek J, Verroust PJ, Willnow TE, Fyfe JC, Nowacki W, Jacobsen C, Moestrup SK, Christensen EI (2002) Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin. J Am Soc Nephrol 13:423–430
  PubMed CAS Google Scholar
• Gekle M, Drumm K, Mildenberger S, Freudinger R, Gassner B, Silbernagl S (1999) Inhibition of Na+-H+ exchange impairs receptor-mediated albumin endocytosis in renal proximal tubule-derived epithelial cells from opossum. J Physiol 520:709–721
  Article PubMed CAS Google Scholar
• Gekle M, Serrano OK, Drumm K, Mildenberger S, Freudinger R, Gassner B, Jansen HW, Christensen EI (2002) NHE3 serves as a molecular tool for cAMP-mediated regulation of receptor-mediated endocytosis. Am J Physiol Renal Physiol 283:F549–F558
  PubMed CAS Google Scholar
• Gekle M, Volker K, Mildenberger S, Freudinger R, Shull GE, Wiemann M (2004) NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo. Am J Physiol Renal Physiol 287:F469–F473
  Article PubMed CAS Google Scholar
• Gonzalez-Villalobos R, Klassen RB, Allen PL, Navar LG, Hammond TG (2005) Megalin binds and internalizes angiotensin II. Am J Physiol Renal Physiol 288:F420–F427
  Article PubMed CAS Google Scholar
• Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (2000) 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 275:25616–25624
  Article PubMed CAS Google Scholar
• Grabowski GA, Hopkin RJ (2003) Enzyme therapy for lysosomal storage disease: principles, practice, and prospects. Annu Rev Genomics Hum Genet 4:403–436
  Article PubMed CAS Google Scholar
• Gräsbeck R, Gordin R, Kantero I, Kuhlbäck B (1960) Selective vitamin B12 malabsorption and proteinuria in young people. Acta Med Scand 167:289–296
  Article PubMed Google Scholar
• Günther W, Lüchow A, Cluzeaud F, Vandewalle A, Jentsch TJ (1998) ClC-5, the chloride channel mutated in Dent's disease, colocalizes with the proton pump in endocytotically active kidney cells. Proc Natl Acad Sci USA 95:8075–8080
  Article PubMed Google Scholar
• Hama H, Saito A, Takeda T, Tanuma A, Xie Y, Sato K, Kazama JJ, Gejyo F (2004) Evidence indicating that renal tubular metabolism of leptin is mediated by megalin but not by the leptin receptors. Endocrinology 145:3935–3940
  Article PubMed CAS Google Scholar
• Hammad SM, Barth JL, Knaak C, Argraves WS (2000) Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem 275:12003–12008
  Article PubMed CAS Google Scholar
• Hammad SM, Stefansson S, Twal WO, Drake CJ, Fleming P, Remaley A, Brewer HBJ, Argraves WS (1999) Cubilin, the endocytic receptor for intrinsic factor-vitamin B12 complex, mediates high-density lipoprotein holoparticle endocytosis. Proc Natl Acad Sci USA 96:10158–10163
  Article PubMed CAS Google Scholar
• Hammes A, Andreassen TK, Spoelgen R, Raila J, Hubner N, Schulz H, Metzger J, Schweigert FJ, Luppa PB, Nykjaer A, Willnow TE (2005) Role of endocytosis in cullular uprake of sex steroids. Cell 122:751–762
  Article PubMed CAS Google Scholar
• He Q, Fyfe JC, Schäffer AA, Kilkenney A, Werner P, Kirkness EF, Henthorn PS (2003) Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome 14:765–777
  Article CAS Google Scholar
• He Q, Madsen M, Kilkenney A, Gregory B, Christensen EI, Vorum H, Hojrup P, Schaffer AA, Kirkness EF, Tanner SM, de la Chapelle A, Giger U, Moestrup SK, Fyfe JC (2005) Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood 106:1447–1453
  Article PubMed CAS Google Scholar
• Hilpert J, Nykjaer A, Jacobsen C, Wallukat G, Nielsen R, Moestrup SK, Haller H, Luft FC, Christensen EI, Willnow TE (1999) Megalin antagonizes activation of the parathyroid hormone receptor. J Biol Chem 274:5620–5625
  Article PubMed CAS Google Scholar
• Hjälm G, Murray E, Crumley G, Harazim W, Lundgren S, Onyango I, Ek B, Larsson M, Juhlin C, Hellman P, Davis H, Åkerström G, Rask L, Morse B (1996) Cloning and sequencing of human gp330, a Ca2+-binding receptor with potential intracellular signaling properties. Eur J Biochem 239:132–137
  Article PubMed Google Scholar
• Hoopes RR, Jr., Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, Simckes A, Tasic V, Toenshoff B, Suchy SF, Nussbaum RL, Scheinman SJ (2005) Dent disease with mutations in OCRL1. Am J Hum Genet 76:260–267
  Article PubMed CAS Google Scholar
• Hryciw DH, Ekberg J, Lee A, Lensink IL, Kumar S, Guggino WB, Cook DI, Pollock CA, Poronnik P (2004) Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells. J Biol Chem 279:54996–55007
  Article PubMed CAS Google Scholar
• Hryciw DH, Wang Y, Devuyst O, Pollock CA, Poronnik P, Guggino WB (2003) Cofilin interacts with ClC-5 and regulates albumin uptake in proximal tubule cell lines. J Biol Chem 278:40169–40176
  Article PubMed CAS Google Scholar
• Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N (2005) The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett 579:773–777
  Article PubMed CAS Google Scholar
• Imerslund O (1960) Idiopathic chronic megaloblastic anemia in children. Acta Paediatr Scand 49(suppl.119):1–115
  Google Scholar
• Inui K, Saito H, Iwata T, Hori R (1988) Aminoglycoside-induced alterations in apical membranes of kidney epithelial cell line (LLC-PK1). Am J Physiol Cell Physiol 254:C251–C257
  CAS Google Scholar
• Kalantry S, Manning S, Haub O, Tomihara-Newberger C, Lee HG, Fangman J, Disteche CM, Manova K, Lacy E (2001) The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain. Nat Genet 27:412–416
  Article PubMed CAS Google Scholar
• Kalatzis V, Antignac C (2003) New aspects of the pathogenesis of cystinosis. Pediatr Nephrol 18:207–215
  PubMed Google Scholar
• Kanalas JJ, Makker SP (1991) Identification of the rat Heymann nephritis autoantigen (GP330) as a receptor site for plasminogen. J Biol Chem 266:10825–10829
  PubMed CAS Google Scholar
• Kerjaschki D, Farquhar MG (1982) The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci USA 79:5557–5561
  Article PubMed CAS Google Scholar
• Kerjaschki D, Farquhar MG (1983) Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med 157:667–686
  Article PubMed CAS Google Scholar
• Klassen RB, Crenshaw K, Kozyraki R, Verroust PJ, Tio L, Atrian S, Allen PL, Hammond TG (2004) Megalin mediates renal uptake of heavy metal metallothionein complexes. Am J Physiol Renal Physiol 287:F393–F403
  Article PubMed CAS Google Scholar
• Kounnas MZ, Chappell DA, Strickland DK, Argraves WS (1993) Glycoprotein 330, a member of the low density lipoprotein receptor family, binds lipoprotein lipase in vitro. J Biol Chem 268:14176–14181
  PubMed CAS Google Scholar
• Kounnas MZ, Loukinova EB, Stefansson S, Harmony JA, Brewer BH, Strickland DK, Argraves WS (1995) Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J Biol Chem 270:13070–13075
  Article PubMed CAS Google Scholar
• Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, Christensen EI, Aminoff M, de la Chapelle A, Krahe R, Verroust PJ, Moestrup SK (1999) The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. Nat Med 5:656–661
  Article PubMed CAS Google Scholar
• Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C, Dautry-Varsat A, Gburek J, Willnow TE, Christensen EI, Moestrup SK (2001) Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci USA 98:12491–12496
  Article PubMed CAS Google Scholar
• Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, Verroust PJ, Moestrup SK (1998) The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region. Blood 91:3593–3600
  PubMed CAS Google Scholar
• Krauss M, Kinuta M, Wenk MR, De Camilli P, Takei K, Haucke V (2003) ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Iγ. J Cell Biol 162:113–124
  Article PubMed CAS Google Scholar
• Kristiansen M, Kozyraki R, Jacobsen C, Nexø E, Verroust PJ, Moestrup SK (1999) Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding. J Biol Chem 274:20540–20544
  Article PubMed CAS Google Scholar
• Larsson M, Hjalm G, Sakwe AM, Engstrom A, Hoglund AS, Larsson E, Robinson RC, Sundberg C, Rask L (2003) Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins. Biochem J 373:381–391
  Article PubMed CAS Google Scholar
• Leheste JR, Rolinski B, Vorum H, Hilpert J, Nykjaer A, Jacobsen C, Aucouturier P, Moskaug J, Otto A, Christensen EI, Willnow TE (1999) Megalin knockout mice as an animal model of low molecular weight proteinuria. Am J Pathol 155:1361–1370
  Article PubMed CAS Google Scholar
• Levine JS, Allen RH, Alpers DH, Seetharam B (1984) Immunocytochemical localization of the intrinsic factor-cobalamin receptor in dog ileum: distribution of intracellular receptor during cell maturation. J Cell Biol 98:1111–1118
  Article PubMed CAS Google Scholar
• Lowe CU, Terrey M, MacLachlan EA (1952) Organic aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation; a clinical entity. AMA Am J Dis Child 83:164–184
  PubMed CAS Google Scholar
• Lundgren S, Carling T, Hjälm G, Juhlin C, Rastad J, Pihlgren U, Rask L, Åkerström G, Hellman P (1997) Tissue distribution of human gp330/megalin, a putative Ca2+-sensing protein. J Histochem Cytochem 45:383–392
  Article PubMed CAS Google Scholar
• Luyckx VA, Leclercq B, Dowland LK, Yu AS (1999) Diet-dependent hypercalciuria in transgenic mice with reduced CLC5 chloride channel expression. Proc Natl Acad Sci USA 96:12174–12179
  Article PubMed CAS Google Scholar
• Madsen KM, Harris RH, Tisher CC (1982) Uptake and intracellular distribution of ferritin in the rat distal convoluted tubule. Kidney Int 21:354–361
  Article PubMed CAS Google Scholar
• Maranda B, Brown D, Bourgoin S, Casanova JE, Vinay P, Ausiello DA, Marshansky V (2001) Intra-endosomal pH-sensitive recruitment of the Arf-nucleotide exchange factor ARNO and Arf6 from cytoplasm to proximal tubule endosomes. J Biol Chem 276:18540–18550
  Article PubMed CAS Google Scholar
• Marino M, Zheng G, Chiovato L, Pinchera A, Brown D, Andrews D, McCluskey RT (2000) Role of megalin (gp330) in transcytosis of thyroglobulin by thyroid cells. A novel function in the control of thyroid hormone release. J Biol Chem 275:7125–7137
  Article PubMed CAS Google Scholar
• Marshansky V, Ausiello DA, Brown D (2002) Physiological importance of endosomal acidification: potential role in proximal tubulopathies. Curr Opin Nephrol Hypertens 11:527–537
  Article PubMed Google Scholar
• McCarthy RA, Barth JL, Chintalapudi MR, Knaak C, Argraves WS (2002) Megalin functions as an endocytic sonic hedgehog receptor. J Biol Chem 277:25660–25667
  Article PubMed CAS Google Scholar
• Mingeot-Leclercq MP, Tulkens PM (1999) Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43:1003–1012
  PubMed CAS Google Scholar
• Moestrup SK, Birn H, Fischer PB, Petersen CM, Verroust PJ, Sim RB, Christensen EI, Nexø E (1996) Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis. Proc Natl Acad Sci USA 93:8612–8617
  Article PubMed CAS Google Scholar
• Moestrup SK, Cui S, Vorum H, Bregengård C, Bjørn SE, Norris K, Gliemann J, Christensen EI (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. J Clin Invest 96:1404–1413
  Article PubMed CAS Google Scholar
• Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH, Brault D, Pontillon F, Goda FO, Christensen EI, Hammond TG, Verroust PJ (1998a) The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins. J Biol Chem 273:5235–5242
  Article PubMed CAS Google Scholar
• Moestrup SK, Nielsen S, Andreasen P, Jørgensen KE, Nykjaer A, Røigaard H, Gliemann J, Christensen EI (1993) Epithelial glycoprotein-330 mediates endocytosis of plasminogen activator-plasminogen activator inhibitor type-1 complexes. J Biol Chem 268:16564–16570
  PubMed CAS Google Scholar
• Moestrup SK, Schousboe I, Jacobsen C, Leheste JR, Christensen EI, Willnow TE (1998b) β2-Glycoprotein-I (apolipoprotein H) and β2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin. J Clin Invest 102:902-909
  Article PubMed CAS Google Scholar
• Morris SM, Tallquist MD, Rock CO, Cooper JA (2002) Dual roles for the Dab2 adaptor protein in embryonic development and kidney transport. EMBO J 21:1555–1564
  Article PubMed CAS Google Scholar
• Muller D, Ankermann T, Stephani U, Kirschstein M, Szelestei T, Luft FC, Willnow TE (2001) Holoprosencephaly and low molecular weight proteinuria: the human homologue of murine megalin deficiency. Am J Kidney Dis 37:624–628
  Article PubMed CAS Google Scholar
• Nagai J, Christensen EI, Morris SM, Willnow TE, Cooper JA, Nielsen R (2005) Mutually dependent localization of megalin and Dab2 in the renal proximal tubule. Am J Physiol Renal Physiol 289:F569–F576
  Article PubMed CAS Google Scholar
• Nagai J, Tanaka H, Nakanishi N, Murakami T, Takano M (2001) Role of megalin in renal handling of aminoglycosides. Am J Physiol Renal Physiol 281:F337–F344
  PubMed CAS Google Scholar
• Nagai M, Meerloo T, Takeda T, Farquhar MG (2003) The adaptor protein ARH escorts megalin to and through endosomes. Mol Biol Cell 14:4984–4996
  Article PubMed CAS Google Scholar
• Norden AG, Lapsley M, Igarashi T, Kelleher CL, Lee PJ, Matsuyama T, Scheinman SJ, Shiraga H, Sundin DP, Thakker RV, Unwin RJ, Verroust P, Moestrup SK (2002) Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome. J Am Soc Nephrol 13:125–133
  PubMed CAS Google Scholar
• Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, Melsen F, Christensen EI, Willnow TE (1999) An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 96:507–515
  Article PubMed CAS Google Scholar
• Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, Verroust PJ, Aminoff M, de la Chapelle A, Moestrup SK, Ray R, Gliemann J, Willnow TE, Christensen EI (2001) Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D3. Proc Natl Acad Sci USA 98:13895–13900
  Article PubMed CAS Google Scholar
• Oleinikov AV, Zhao J, Makker SP (2000) Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic receptor gp600/megalin. Biochem J 347:613–621
  Article PubMed CAS Google Scholar
• Orlando RA, Kerjaschki D, Kurihara H, Biemesderfer D, Farquhar MG (1992) gp330 associates with a 44-kDa protein in the rat kidney to form the Heymann nephritis antigenic complex. Proc Natl Acad Sci USA 89:6698–6702
  Article PubMed CAS Google Scholar
• Orlando RA, Rader K, Authier F, Yamazaki H, Posner BI, Bergeron JJ, Farquhar MG (1998) Megalin is an endocytic receptor for insulin. J Am Soc Nephrol 9:1759–1766
  PubMed CAS Google Scholar
• Oyama Y, Takeda T, Hama H, Tanuma A, Iino N, Sato K, Kaseda R, Ma M, Yamamoto T, Fujii H, Kazama JJ, Odani S, Terada Y, Mizuta K, Gejyo F, Saito A (2005) Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules. Lab Invest 85:522–531
  Article PubMed CAS Google Scholar
• Petersen HH, Hilpert J, Militz D, Zandler V, Jacobsen C, Roebroek AJ, Willnow TE (2003) Functional interaction of megalin with the megalin binding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule. J Cell Sci 116:453–461
  Article PubMed CAS Google Scholar
• Picollo A, Pusch M (2005) Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. Nature 436:420–423
  Article PubMed CAS Google Scholar
• Piwon N, Gunther W, Schwake M, Bosl MR, Jentsch TJ (2000) CIC-5 Cl−-channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 408:369–373
  Article PubMed CAS Google Scholar
• Ranganathan S, Knaak C, Morales CR, Argraves WS (1999) Identification of low density lipoprotein receptor-related protein-2/megalin as an endocytic receptor for seminal vesicle secretory protein II. J Biol Chem 274:5557–5563
  Article PubMed CAS Google Scholar
• Raychowdhury R, Niles JL, McCluskey RT, Smith JA (1989) Autoimmune target in Heymann nephritis is a glycoprotein with homology to the LDL receptor. Science 244:1163–1165
  Article PubMed CAS Google Scholar
• Rosenblatt DS, Fenton WA (1999) Inborn errors of cobalamin metabolism. In: Banerjee R (ed) Chemistry and Biochemistry of Vitamin B12. Wiley and Sons, New York, pp 367–384
  Google Scholar
• Sahali D, Mulliez N, Chatelet F, Dupuis R, Ronco P, Verroust P (1988) Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies. J Exp Med 167:213–218
  Article PubMed CAS Google Scholar
• Sahali D, Mulliez N, Chatelet F, Laurent Winter C, Citadelle D, Roux C, Ronco P, Verroust P (1992) Coexpression in humans by kidney and fetal envelopes of a 280 kDa-coated pit-restricted protein. Similarity with the murine target of teratogenic antibodies. Am J Pathol 140:33–44
  PubMed CAS Google Scholar
• Saito A, Nagai R, Tanuma A, Hama H, Cho K, Takeda T, Yoshida Y, Toda T, Shimizu F, Horiuchi S, Gejyo F (2003) Role of megalin in endocytosis of advanced glycation end products: implications for a novel protein binding to both megalin and advanced glycation end products. J Am Soc Nephrol 14:1123–1131
  Article PubMed CAS Google Scholar
• Saito A, Pietromonaco S, Loo AK, Farquhar MG (1994) Complete cloning and sequencing of rat gp330/“megalin,” a distinctive member of the low density lipoprotein receptor gene family. Proc Natl Acad Sci USA 91:9725–9729
  Article PubMed CAS Google Scholar
• Scheel O, Zdebik AA, Lourdel S, Jentsch TJ (2005) Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature 436:424–427
  Article PubMed CAS Google Scholar
• Scheinman SJ (1998) X-linked hypercalciuric nephrolithiasis: clinical syndromes and chloride channel mutations. Kidney Int 53:3-17
  Article PubMed CAS Google Scholar
• Schmitz C, Hilpert J, Jacobsen C, Boensch C, Christensen EI, Luft FC, Willnow TE (2002) Megalin deficiency offers protection from renal aminoglycoside accumulation. J Biol Chem 277:618–622
  Article PubMed CAS Google Scholar
• Seetharam B, Christensen EI, Moestrup SK, Hammond TG, Verroust PJ (1997) Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor. J Clin Invest 99:2317–2322
  Article PubMed CAS Google Scholar
• Silverblatt FJ, Kuehn C (1979) Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney Int 15:335–345
  Article PubMed CAS Google Scholar
• Sousa MM, Norden AG, Jacobsen C, Willnow TE, Christensen EI, Thakker RV, Verroust PJ, Moestrup SK, Saraiva MJ (2000) Evidence for the role of megalin in renal uptake of transthyretin. J Biol Chem 275:38176–38181
  Article PubMed CAS Google Scholar
• Spoelgen R, Hammes A, Anzenberger U, Zechner D, Andersen OM, Jerchow B, Willnow TE (2005) LRP2/megalin is required for patterning of the ventral telencephalon. Development 132:405–414
  Article PubMed CAS Google Scholar
• Stefansson S, Chappell DA, Argraves KM, Strickland DK, Argraves WS (1995a) Glycoprotein 330/low density lipoprotein receptor-related protein-2 mediates endocytosis of low density lipoproteins via interaction with apolipoprotein B100. J Biol Chem 270:19417–19421
  Article PubMed CAS Google Scholar
• Stefansson S, Kounnas MZ, Henkin J, Mallampalli RK, Chappell DA, Strickland DK, Argraves WS (1995b) gp330 on type II pneumocytes mediates endocytosis leading to degradation of pro-urokinase, plasminogen activator inhibitor-1 and urokinase-plasminogen activator inhibitor-1 complex. J Cell Sci 108:2361–2368
  PubMed CAS Google Scholar
• Straus W (1964) Occurrence of phagosomes and phago-lysosomes in different segments of the nephron in relation to the reabsorption, transport, digestion and extrusion of intravenously injected horseradish peroxidase. J Cell Biol 21:295–308
  Article PubMed CAS Google Scholar
• Suchy SF, Olivos-Glander IM, Nussabaum RL (1995) Lowe syndrome, a deficiency of phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Hum Mol Genet 4:2245–2250
  Article PubMed CAS Google Scholar
• Takeda T, Yamazaki H, Farquhar MG (2003) Identification of an apical sorting determinant in the cytoplasmic tail of megalin. Am J Physiol Cell Physiol 284:C1105–C1113
  PubMed CAS Google Scholar
• Tanner SM, Li Z, Bisson R, Acar C, Oner C, Oner R, Cetin M, Abdelaal MA, Ismail EA, Lissens W, Krahe R, Broch H, Grasbeck R, de la Chapelle A (2004) Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East. Hum Mutat 23:327–333
  Article PubMed CAS Google Scholar
• Thurberg BL, Rennke H, Colvin RB, Dikman S, Gordon RE, Collins AB, Desnick RJ, O'Callaghan M (2002) Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62:1933–1946
  Article PubMed CAS Google Scholar
• Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, van't Hoff W, Antignac C (1998) A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet 18:319–324
  Article PubMed CAS Google Scholar
• Vandewalle A, Farman N, Morin JP, Fillastre JP, Hatt PY, Bonvalet JP (1981) Gentamicin incorporation along the nephron: autoradiographic study on isolated tubules. Kidney Int 19:529–539
  Article PubMed CAS Google Scholar
• Verroust PJ, Birn H, Nielsen R, Kozyraki R, Christensen EI (2002) The tandem endocytic receptors megalin and cubilin are important proteins in renal pathology. Kidney Int 62:745–756
  Article PubMed CAS Google Scholar
• Wahlstedt-Froberg V, Pettersson T, Aminoff M, Dugue B, Grasbeck R (2003) Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption. Pediatr Nephrol 18:417–421
  PubMed Google Scholar
• Wang SS, Devuyst O, Courtoy PJ, Wang XT, Wang H, Wang Y, Thakker RV, Guggino S, Guggino WB (2000) Mice lacking renal chloride channel, CLC-5, are a model for Dent's disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. Hum Mol Genet 9:2937–2945
  Article PubMed CAS Google Scholar
• Willnow TE (1998) Receptor-associated protein (RAP): a specialized chaperone for endocytic receptors. Biol Chem 379:1025–1031
  PubMed CAS Google Scholar
• Willnow TE, Armstrong SA, Hammer RE, Herz J (1995) Functional expression of low density lipoprotein receptor- related protein is controlled by receptor-associated protein in vivo. Proc Natl Acad Sci USA 92:4537–4541
  Article PubMed CAS Google Scholar
• Willnow TE, Goldstein JL, Orth K, Brown MS, Herz J (1992) 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 267:26172–26180
  PubMed CAS Google Scholar
• Willnow TE, Hilpert J, Armstrong SA, Rohlmann A, Hammer RE, Burns DK, Herz J (1996a) Defective forebrain development in mice lacking gp330/megalin. Proc Natl Acad Sci USA 93:8460–8464
  Article PubMed CAS Google Scholar
• Willnow TE, Rohlmann A, Horton J, Otani H, Braun JR, Hammer RE, Herz J (1996b) RAP, a specialized chaperone, prevents ligand-induced ER retention and degradation of LDL receptor-related endocytic receptors. EMBO J 15:2632–2639
  PubMed CAS Google Scholar
• Wrong OM, Norden AG, Feest TG (1994) Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. QJM 87:473–493
  PubMed CAS Google Scholar
• Xu D, Kozyraki R, Newman TC, Fyfe JC (1999) Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption. Blood 94:3604–3606
  PubMed CAS Google Scholar
• Yammani RR, Seetharam S, Dahms NM, Seetharam B (2003) Transcobalamin II receptor interacts with megalin in the renal apical brush border membrane. J Membr Biol 193:57–66
  Article PubMed CAS Google Scholar
• Yammani RR, Seetharam S, Seetharam B (2001) Cubilin and megalin expression and their interaction in the rat intestine: effect of thyroidectomy. Am J Physiol Endocrinol Metab 281:E900–E907
  PubMed CAS Google Scholar
• Yammani RR, Sharma M, Seetharam S, Moulder JE, Dahms NM, Seetharam B (2002) Loss of albumin and megalin binding to renal cubilin in rats results in albuminuria after total body irradiation. Am J Physiol Regul Integr Comp Physiol 283:R339–R346
  PubMed CAS Google Scholar
• Zhai XY, Nielsen R, Birn H, Drumm K, Mildenberger S, Freudinger R, Moestrup SK, Verroust PJ, Christensen EI, Gekle M (2000) Cubilin- and megalin-mediated uptake of albumin in cultured proximal tubule cells of opossum kidney. Kidney Int 58:1523–1533
  Article PubMed CAS Google Scholar
• Zheng G, Bachinsky DR, Stamenkovic I, Strickland DK, Brown D, Andres G, McCluskey RT (1994) Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/α2MR, and the receptor-associated protein (RAP). J Histochem Cytochem 42:531–542
  Article PubMed CAS Google Scholar
• Zheng G, Marino, Zhao J, McCluskey RT (1998) Megalin (gp330): a putative endocytic receptor for thyroglobulin (Tg). Endocrinology 139:1462–1465
  Article PubMed CAS Google Scholar

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