ライフサイエンスコーパス: cubilin

1 aused by defect of a gene product other than cubilin.

2 ubule (PT) multiligand receptors megalin and cubilin.

3 of the main scavenger receptors, MEGALIN and CUBILIN.

4 ugh the multiligand receptor complex megalin-cubilin.

5 studies of AMN function and coevolution with cubilin.

6 , identifying p400 as the murine ortholog of cubilin.

7 the endocytic receptors megalin (gp330) and cubilin.

8 o inhibit albumin binding to both regions of cubilin.

9 y a role in the intracellular trafficking of cubilin.

10 sulted in reduced cell surface expression of cubilin.

11 Working in concert with megalin and cubilin, a nonselective multireceptor complex that predo

12 In cubilin transfectants, cubilin accumulated in early biosynthetic compartments.

13 that cubilin and AMN are subunits of a novel cubilin/AMN (cubam) complex, where AMN binds to the amin

14 own, suggesting evolutionary conservation of Cubilin/AMN co-receptors function from flies to humans.

15 Furthermore, we found that Cubilin/AMN-mediated protein reabsorption is required fo

16 to albumin overload prompted an increase in CUBILIN, AMNIONLESS and CLCN5 gene expression.

17 overload first acts on the expression of the cubilin-amnionless (CUBAM) complex in these cells, then

18 in EECs of the nutrient receptor triad, LRP2-cubilin-amnionless, changes significantly.

19 Yolk components endocytosed by LRP2-cubilin-amnionless, preformed and newly formed lipid dro

20 eral ligands and interacting proteins in the cubilin-amnionless-megalin complex that are involved in

21 merase chain reaction-amplified fragments of cubilin, an endocytic receptor of molecular mass 460 kDa

22 These data indicate that cubilin and AMN are subunits of a novel cubilin/AMN (cub

23 Here we show that cubilin and AMN colocalize in the endocytic apparatus of

24 ophila genes encoding orthologs of mammalian cubilin and amnionless (AMN), two major receptors for pr

25 of 2 genes encoding the epithelial proteins: cubilin and amnionless (AMN).

26 ere AMN binds to the amino-terminal third of cubilin and directs subcellular localization and endocyt

27 Cubilin and megalin exhibited coincident patterns of mRN

28 Tracer endocytosis by nephrocytes required Cubilin and reflected size selectivity analogous to that

29 Cubilin antibodies inhibit HDL endocytosis by the endode

30 pendence of ligand binding or the ability of cubilin antiserum to inhibit ligand binding to the 113-r

31 ependence or inhibition of ligand binding by cubilin antiserum.

32 Megalin and cubilin are cooperating receptors essential to the proxi

33 These studies show the great potential of cubilin as a new target for the delivery of B(12) based

34 ntrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 kno

35 This is consistent with cubilin being an endogenous partner of galectin-3 at the

36 ver, in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to the cell surfac

37 ther AMN or a truncated IF-cobalamin-binding cubilin construct, neither protein alone conferred ligan

38 These results indicate that (a) cubilin contains two distinct regions that bind both IF-

39 Cubilin (Cubn) is a multiligand endocytic receptor criti

40 Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS.

41 the C3 epimer of 25(OH)D3 [3-epi-25(OH)D3]; cubilin (CUBN) with 25(OH)D3; 25-hydroxylase (CYP2R1) wi

42 umans, AMN has been genetically connected to Cubilin (CUBN), a multi-ligand scavenger receptor expres

43 Cubilin deficiency leads to urinary loss of albumin and

44 he basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery ba

45 electrophoresis demonstrated that in megalin/cubilin-deficient mice an increased amount of (99m)Tc-DM

46 We have used megalin/cubilin-deficient mice produced by gene knockout to dete

47 The reduced renal uptake in megalin/cubilin-deficient mice was accompanied by an increase in

48 Control or megalin/cubilin-deficient mice were injected intravenously with

49 In megalin/cubilin-deficient mice, we observed decreased uptake and

50 MSA was identified in scintigrams of megalin/cubilin-deficient mice.

51 robe, a B(12) conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell l

52 orrelating with a reduction in renal megalin/cubilin expression in knockout mice to about 10% of norm

53 ssibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase

54 mbryo yolk-sac endoderm, a prominent site of cubilin expression.

55 min but not IF-Cbl binding to the N-terminal cubilin fragment that included the eight EGF-like repeat

56 es of seven tryptic peptides were similar to cubilin from rats, humans, and dogs, identifying p400 as

57 Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cu

58 Amnionless (AMN) and cubilin gene products appear to be essential functional

59 ene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proxim

60 Since cubilin has been reported to bind the endocytic receptor

61 Cubilin has recently been shown to function as an endocy

62 ressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly.

63 Moreover, cubilin HT mice displayed significantly decreased blood

64 mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficienc

65 l) from the blood increased significantly in cubilin HT mice.

66 otted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated protein.

67 interface and suggests an important role for cubilin in uNK cell function.

68 us validating the system for analysis of AMN-cubilin interactions.

69 Cubilin is a high molecular weight multiligand receptor

70 Cubilin is an endocytic receptor highly expressed in ren

71 and proteinuria occurs in 50% of cases since cubilin is coreceptor for both the intestinal vitamin B(

72 ot uNK cells, implying that yolk sac-derived cubilin is endocytosed by uNK cells via galectin-3.

73 These findings, coupled with the fact that cubilin is expressed in kidney proximal tubules, suggest

74 DL, or apoA-I, it was found to copurify with cubilin isolated by HDL-Sepharose affinity chromatograph

75 Inhibiting cubilin led to a reduction in albumin uptake, highlighti

76 Megalin and cubilin levels detected by immunochemiluminescence were

77 lly increased internalization of the megalin-cubilin ligand albumin as well as the fluid phase marker

78 alpha1-microglobulin, an established megalin/cubilin ligand.

79 min and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apo

80 ation of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experime

81 godeoxynucleotides resulted in inhibition of cubilin-mediated endocytosis of HDL.

82 in and accumulates in the kidneys by megalin/cubilin-mediated endocytosis of the (99m)Tc-DMSA protein

83 Cubilin-mediated HDL endocytosis is inhibitable by HDL(2

84 (IF) vitamin B(12) ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex o

85 -mediated endocytosis, involving megalin and cubilin, mediates renal proximal-tubular reabsorption an

86 We show that these cells express cubilin, megalin, ClC-5, amnionless and Dab2, which are

87 ors, ligands and interacting proteins in the cubilin-megalin multiligand endocytic receptor complex a

88 rk Pathway analysis included 12 genes in the cubilin-megalin multiligand endocytic receptor complex.

89 In situ hybridization revealed cubilin mRNA in yolk sac epithelium but not uNK cells, i

90 human Imerslund-Grasbeck syndrome caused by cubilin mutations.

91 Cubilin occurred in yolk sac epithelium throughout pregn

92 mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane.

93 visceral yolk sac of RFC1-/- embryos, while cubilin protein was widely misexpressed.

94 ent transmembrane and cytoplasmic domains in cubilin raises questions as to the means by which it can

95 DMSA is thus critically dependent on megalin/cubilin receptor function and therefore is a marker of p

96 n receptor-expressing CA20948 and megalin or cubilin receptor-expressing BN-16 cells, in the absence

97 Cubilin recognizes intrinsic factor (IF)-cobalamin and v

98 a and that normal brush-border expression of cubilin requires the activity of an accessory protein.

99 ation mouse embryos, where interactions with cubilin result in nutrient endocytosis, and it may be im

100 d progressive loss of expression of megalin, cubilin, sodium-glucose cotransporter 2, and type IIa so

101 e used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular e

102 DL affinity chromatography and identified as cubilin, the recently described endocytic receptor for i

103 demonstrate that megalin acts together with cubilin to mediate HDL endocytosis and further suggest t

104 bility that megalin acts in conjunction with cubilin to mediate HDL endocytosis.

105 nsfected with AMN and the cubilin construct, cubilin trafficked to the cell surface and endosomes, an

106 In cubilin transfectants, cubilin accumulated in early bios

107 Unexpectedly, cubilin was found only in perforin-containing granules o

108 ding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN,

109 The measured levels of cubilin were normal for all patients.

110 subcellular localization and endocytosis of cubilin with its ligand.

111 n associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (U