From bowel to kidneys: The role of cubilin in physiology and disease

Nephrology Dialysis Transplantation

Volumn 28, Issue 2, 2013, Pages 274-281

  Christensen, Erik I ^a   Nielsen, Rikke ^a   Birn, Henrik ^a  

^a AARHUS UNIVERSITY   (Denmark)

Author keywords

albuminuria; Imerslund Gr sbeck syndrome; low molecular weight proteinuria; receptor mediated endocytosis; vitamin B12

Indexed keywords

ALBUMIN; AMNIONLESS; CUBILIN; CYANOCOBALAMIN; INTRINSIC FACTOR; MEGALIN; MEMBRANE PROTEIN; PLASMA PROTEIN; TRANSFERRIN; UNCLASSIFIED DRUG; VITAMIN D BINDING PROTEIN;

ACUTE KIDNEY FAILURE; ALBUMINURIA; CHRONIC KIDNEY DISEASE; ENDOCYTOSIS; ENTEROPATHY; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; IMERSLUND GRASBECK SYNDROME; INTESTINE ABSORPTION; KIDNEY DISEASE; KIDNEY PROXIMAL TUBULE; KIDNEY TUBULE ABSORPTION; MEGALOBLASTIC ANEMIA; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEFICIENCY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; URINARY TRACT DISEASE;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; INTESTINAL ABSORPTION; KIDNEY TUBULES, PROXIMAL; RECEPTORS, CELL SURFACE; RENAL INSUFFICIENCY, CHRONIC; VITAMIN B 12 DEFICIENCY;

EID: 84874527043     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfs565     Document Type: Review

References (90)

1. Minot GR, Murphy WP. Treatment of pernicious anemia by a special diet. J Am Med Assoc 1926; 87: 470-476
2. Castle WB, Heath CW, Strauss MB et al. Observations on the etiologic relationship of Achylia gastrica to pernicious anemia. VI. The site of the interaction of food (Extrinsic) and gastric (Intrinsic) factors; failure of in vitro incubation to produce a thermostable hematopoietic principle. Am J Med Sci 1937; 194: 618-625
3. Herbert V. Mechanism of intrinsic factor action in everted sacs of rat small intestine. J Clin Invest 1959; 38: 102-109
4. Seetharam B, Alpers DH. Absorption and transport of cobalamin (vitamin B12). Annu Rev Nutr 1982; 2:343-369
5. Imerslund O. Idiopathic chronic megaloblastic anemia in children. Acta Paediatr Scand 1960; 49(Suppl. 119): 1-115
6. Gräsbeck R, Gordin R, Kantero I et al. Selective vitamin B12 malabsorption and proteinuria in young people. Acta Med Scand 1960; 167: 289-296
7. Chatelet F, Brianti E, Ronco P et al. Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. I. Renal distribution. Am J Pathol 1986; 122: 500-511 (Pubitemid 16017671)
8. Sahali D, Mulliez N, Chatelet F et al. 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 1988; 167: 213-218 (Pubitemid 18093704)
9. Chatelet F, Brianti E, Ronco P et al. Ultrastructural localization by monoclonal antibodies of brush border antigens expressed by glomeruli. II. Extrarenal distribution. Am J Pathol 1986; 122: 512-519 (Pubitemid 16017672)
10. Seetharam B, Levine JS, Ramasamy M et al. Purification, properties, and immunochemical localization of a receptor for Intrinsic Factor-Cobalamin complex in the rat kidney. J Biol Chem 1988; 263: 4443-4449 (Pubitemid 18096628)
11. Seetharam B, Christensen EI, Moestrup SK et al. Identification of rat yolk sac target protein of teratogenic antibodies, gp280, as intrinsic factor-cobalamin receptor. J Clin Invest 1997; 99: 2317-2322 (Pubitemid 27227706)
12. Birn H, Verroust PJ, Nexø E et al. Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein. J Biol Chem 1997; 272: 26497-26504 (Pubitemid 27458869)
13. Moestrup SK, Kozyraki R, Kristiansen M et al. The intrinsic factorvitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins. J Biol Chem 1998; 273: 5235-5242 (Pubitemid 28108687)
14. Kozyraki R, Kristiansen M, Silahtaroglu A et al. 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 1998; 91: 3593-3600 (Pubitemid 28225724)
15. Aminoff M, Carter JE, Chadwick RB et al. Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1. Nat Genet 1999; 21: 309-313 (Pubitemid 29124941)
16. Fyfe JC, Ramanujam KS, Ramaswamy K et al. Defective brushborder expression of intrinsic factor-cobalamin receptor in canine inherited intestinal cobalamin malabsorption. J Biol Chem 1991; 266: 4489-4494 (Pubitemid 21909383)
17. Fyfe JC, Giger U, Hall CA et al. Inherited selective intestinal cobalamin malabsorption and cobalamin deficiency in dogs. Pediatr Res 1991; 29: 24-31
18. Xu D, Kozyraki R, Newman TC et al. Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption. Blood 1999; 94: 3604-3606 (Pubitemid 29536157)
19. Tanner SM, Aminoff M, Wright FA et al. Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia. Nat Genet 2003; 33: 426-429 (Pubitemid 36278863)
20. He Q, Fyfe JC, Schäffer AA et al. Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q. Mamm Genome 2003; 14: 765-777
21. He Q, Madsen M, Kilkenney A et al. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood 2005; 106: 1447-1453 (Pubitemid 41129614)
22. Fyfe JC, Madsen M, Hojrup P et al. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. Blood 2004; 103: 1573-1579 (Pubitemid 38268944)
23. Coudroy G, Gburek J, Kozyraki R et al. Contribution of cubilin and amnionless to processing and membrane targeting of cubilin-amnionless complex. J Am Soc Nephrol 2005; 16: 2330-2337 (Pubitemid 41725050)
24. Bork P, Beckmann G. The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol 1993; 231: 539-545 (Pubitemid 23188276)
25. Kristiansen M, Kozyraki R, Jacobsen C et al. Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding. J Biol Chem 1999; 274: 20540-20544
26. Yammani RR, Seetharam S, Seetharam B. Identification and characterization of two distinct ligand binding regions of cubilin. J Biol Chem 2001; 276: 44777-44784
27. Andersen CB, Madsen M, Storm T et al. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. Nature 2010; 464: 445-448
28. Christensen EI, Birn H, Storm T et al. Endocytic receptors in the renal proximal tubule. Physiology (Bethesda) 2012; 27: 223-236
29. Sahali D, Mulliez N, Chatelet F et al. Comparative immunochemistry and ontogeny of two closely related coated pit proteins. The 280-kd target of teratogenic antibodies and the 330-kd target of nephritogenic antibodies. Am J Pathol 1993; 142: 1654-1667 (Pubitemid 24058151)
30. Ahuja R, Yammani R, Bauer JA et al. Interactions of cubilin with megalin and the product of the amnionless gene (AMN): effect on its stability. Biochem J 2008; 410: 301-308 (Pubitemid 351346188)
31. Amsellem S, Gburek J, Hamard G et al. Cubilin Is Essential for Albumin Reabsorption in the Renal Proximal Tubule. J Am Soc Nephrol 2010; 21: 1859-1867
32. Storm T, Tranebjærg L, Frykholm C et al. 'Renal phenotypic investigations of megalin-deficient patients': Novel insights into tubular proteinuria and albumin filtration. Nephrol Dial Transplant 2012, in press
33. Levine JS, Allen RH, Alpers DH et al. Immunocytochemical localization of the intrinsic factor-cobalamin receptor in dog-ileum: distribution of intracellular receptor during cell maturation. J Cell Biol 1984; 98: 1111-1118 (Pubitemid 14166545)
34. Prabakaran T, Christensen EI, Nielsen R et al. Cubilin is expressed in rat and human glomerular podocytes. Nephrol Dial Transplant 2012; 27: 3156-3159
35. Hammad SM, Barth JL, Knaak C et al. Megalin acts in concert with cubilin to mediate endocytosis of high density lipoproteins. J Biol Chem 2000; 275: 12003-12008 (Pubitemid 30237773)
36. Tauris J, Christensen EI, Nykjaer A et al. Cubilin and megalin colocalize in the neonatal inner ear. Audiol Neurootol 2009; 14: 267-278
37. Tomihara-Newberger C, Haub O, Lee HG et al. The amn gene product is required in extraembryonic tissues for the generation of middle primitive streak derivatives. Dev Biol 1998; 204: 34-54 (Pubitemid 28563863)
38. Kalantry S, Manning S, Haub O et al. The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain. Nat Genet 2001; 27: 412-416 (Pubitemid 32268422)
39. Strope S, Rivi R, Metzger T et al. Mouse amnionless, which is required for primitive streak assembly, mediates cell-surface localization and endocytic function of cubilin on visceral endoderm and kidney proximal tubules. Development 2004; 131: 4787-4795 (Pubitemid 39433465)
40. Storm T, Emma F, Verroust PJ et al. A patient with cubilin deficiency. N Engl J Med 2011; 364: 89-91
41. Pedersen GA, Chakraborty S, Steinhauser AL et al. AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic 2010; 11: 706-720
42. Christensen EI, Verroust PJ, Nielsen R. Receptor-mediated endocytosis in renal proximal tubule. Pflugers Arch 2009; 458: 1039-1048
43. Birn H, Fyfe JC, Jacobsen C et al. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption. J Clin Invest 2000; 105: 1353-1361 (Pubitemid 30322401)
44. Zhai XY, Nielsen R, Birn H et al. Cubilin-and megalin-mediated uptake of albumin in cultured proximal tubule cells of opossum kidney. Kidney Int 2000; 58: 1523-1533
45. Weyer K, Storm T, Shan J et al. Mouse model of proximal tubule endocytic dysfunction. Nephrol Dial Transplant 2011; 26: 3446-3451
46. Nielsen R, Christensen EI. Proteinuria and events beyond the slit. Pediatr Nephrol 2010; 25: 813-822
47. Nykjaer A, Fyfe JC, Kozyraki R et al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3). Proc Natl Acad Sci USA 2001; 98: 13895-13900 (Pubitemid 33115995)
48. Kozyraki R, Fyfe J, Kristiansen M et al. The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. Nat Med 1999; 5: 656-661 (Pubitemid 29289429)
49. Kozyraki R, Fyfe J, Verroust PJ et al. Megalin-dependent cubilinmediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc Natl Acad Sci USA 2001; 98: 12491-12496 (Pubitemid 33019973)
50. Nykjær A, Dragun D, Walther D et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell 1999; 96: 507-515 (Pubitemid 29106838)
51. Smith BT, Mussell JC, Fleming PA et al. Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation. BMC Dev Biol 2006; 6:30:30
52. Grasbeck R. Imerslund-Grasbeck syndrome (selective vitamin B(12) malabsorption with proteinuria). Orphanet J Rare Dis 2006; 1: 17.
53. Tanner SM, Sturm AC, Baack EC et al. Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns. Orphanet J Rare Dis 2012; 7: 56
54. Tanner SM, Li Z, Bisson R et al. 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 2004; 23: 327-333 (Pubitemid 38461514)
55. Bouchlaka C, Maktouf C, Mahjoub B et al. Genetic heterogeneity of megaloblastic anaemia type 1 in Tunisian patients. J Hum Genet 2007; 52: 262-270
56. Hauck FH, Tanner SM, Henker J et al. Imerslund-Grasbeck syndrome in a 15-year-old German girl caused by compound heterozygous mutations in CUBN. Eur J Pediatr 2008; 167: 671-675 (Pubitemid 351503504)
57. Wahlstedt-Froberg V, Pettersson T, Aminoff M et al. Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption. Pediatr Nephrol 2003; 18: 417-421 (Pubitemid 36798482)
58. Ovunc B, Otto EA, Vega-Warner V et al. Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria. J Am Soc Nephrol 2011; 22: 1815-1820
59. Laxminarayana KP, Yeshvanth SK, Shetty JK et al. Unusual cause of childhood anemia: imerslund grasbeck syndrome. J Lab Physicians 2011; 3: 113-115
60. Densupsoontorn N, Sanpakit K, Vijarnsorn C et al. Imerslund-Grasbeck syndrome: new mutation in amnionless. Pediatr Int 2012; 54: e19-e21
61. Broch H, Imerslund O, Monn E et al. Imerslund-Grasbeck anemia. A long-term follow-up study. Acta Paediatr Scand 1984; 73: 248-253 (Pubitemid 14192660)
62. Liang DC, Hsu HC, Huang FY et al. Imerslund-Grasbeck syndrome in two brothers: renal biopsy and ultrastructural findings. Pediatr Hematol Oncol 1991; 8: 361-365
63. Luder AS, Tanner SM, de la Chapelle A et al. Amnionless (AMN) mutations in Imerslund-Grasbeck syndrome may be associated with disturbed vitamin B(12) transport into the CNS. J Inherit Metab Dis 2008.
64. Levey AS, de Jong PE, Coresh J et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int 2011; 80: 17-28
65. Boger CA, Chen MH, Tin A et al. CUBN is a gene locus for albuminuria. J Am Soc Nephrol 2011; 22: 555-570
66. Reznichenko A, Snieder H, van den Born J et al. CUBN as a novel locus for end-stage renal disease: insights from renal transplantation. PLoS One 2012; 7: e36512.
67. Schreiber A, Theilig F, Schweda F et al. Acute endotoxemia in mice induces downregulation of megalin and cubilin in the kidney. Kidney Int 2012; 82: 53-59.
68. Vinuesa E, Sola A, Jung M et al. Lipocalin-2-induced renal regeneration depends on cytokines. Am J Physiol Renal Physiol 2008; 295: F1554-F1562
69. Kim HJ, Moradi H, Yuan J et al. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol Renal Physiol 2009; 296: F1297-F1306
70. Vinge L, Lees GE, Nielsen R et al. The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant 2010; 25: 2458-2467
71. Thrailkill KM, Nimmo T, Bunn RC et al. Microalbuminuria in type 1 diabetes is associated with enhanced excretion of the endocytic multiligand receptors megalin and cubilin. Diabetes Care 2009; 32: 1266-1268
72. Ogasawara S, Hosojima M, Kaseda R et al. Significance of urinary full-length and ectodomain forms of megalin in patients with type 2 diabetes. Diabetes Care 2012; 35: 1112-1118
73. Jouret F, Bernard A, Hermans C et al. Cystic fibrosis is associated with a defect in apical receptor-mediated endocytosis in mouse and human kidney. J Am Soc Nephrol 2007; 18: 707-718 (Pubitemid 46434488)
74. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol 2006; 17: 2974-2984 (Pubitemid 44707757)
75. Theilig F. Spread of glomerular to tubulointerstitial disease with a focus on proteinuria. Ann Anat 2010; 192: 125-132
76. Christensen EI, Nielsen R, Birn H. Renal filtration, transport, and metabolism of albumin and albuminuria. In: Alpern RJ, Moe OW, Caplan M (eds). Seldin and Giebisch's The Kidney: Physiology and Pathophysiology. Elsevier, 2013, pp. 2453-2471
77. Birn H, Christensen EI. Renal albumin absorption in physiology and pathology. Kidney Int 2006; 69: 440-449 (Pubitemid 43164434)
78. Liu J, Li K, He Y et al. Anticubilin antisense RNA ameliorates adriamycin-induced tubulointerstitial injury in experimental rats. Am J Med Sci 2011; 342: 494-502
79. Birn H, Leboulleux M, Moestrup SK et al. 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. The Netherlands: Kluwer, 2003, pp. 37-48
80. Li M, Balamuthusamy S, Simon EE et al. Silencing megalin and cubilin genes inhibits myeloma light chain endocytosis and ameliorates toxicity in human renal proximal tubule epithelial cells. Am J Physiol Renal Physiol 2008; 295: F82-F90
81. Basnayake K, Ying WZ, Wang PX et al. Immunoglobulin light chains activate tubular epithelial cells through redox signaling. J Am Soc Nephrol 2010; 21: 1165-1173
82. Gburek J, Birn H, Verroust PJ et al. Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin. Am J Physiol Renal Physiol 2003; 285: F451-F458 (Pubitemid 37010855)
83. Gburek J, Verroust PJ, Willnow TE et al. Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin. J Am Soc Nephrol 2002; 13: 423-430 (Pubitemid 34110430)
84. Christensen EI, Devuyst O, Dom G et al. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci USA 2003; 100: 8472-8477 (Pubitemid 36842569)
85. Piwon N, Gunther W, Schwake M et al. CIC-5 Cl?-channel disruption impairs endocytosis in a mouse model for Dent's disease. Nature 2000; 408: 369-373
86. Ramos-Lopez E, Lange B, Penna-Martinez M et al. The role of cubilin gene polymorphisms and their influence on 25(OH)D3 and 1,25(OH)2D3 plasma levels in type 1 diabetes patients. J Steroid Biochem Mol Biol 2010; 121: 442-444
87. Franke B, Vermeulen SH, Steegers-Theunissen RP et al. An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (CUBN) and tRNA aspartic acid methyltransferase 1 (TRDMT1). Birth Defects Res A Clin Mol Teratol 2009; 85: 216-226
88. Seested T, Appa RS, Jacobsen C et al. Recombinant activated factor VII is reabsorbed in renal proximal tubules and is a ligand to megalin and cubilin. Nephron Exp Nephrol 2011; 117: e82-e92
89. Batuman V, Verroust PJ, Navar GL et al. Myeloma light chains are ligands for cubilin (gp280). Am J Physiol 1998; 275: F246-F254
90. Burmeister R, Boe IM, Nykjaer A et al. A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney. J Biol Chem 2001; 276: 13295-13301