ライフサイエンスコーパス: CD-MPR

1 In addition, CD-MPR binding affinities are modulated by divalent cati

2 ouble mutants, mice lacking IGF2R/CI-MPR and CD-MPR survive in an IGF-II null background at a very lo

3 nt mannose 6-phosphate receptors (CI-MPR and CD-MPR) for high mannose-type N-glycans of defined struc

4 ion of phosphorylated glycans by the CI- and CD-MPRs has implications for understanding the biosynthe

5 A detailed comparison of the available CD-MPR structures reveals the positional invariability o

6 of the extracytoplasmic domain of the bovine CD-MPR (residues 3-154) complexed with mannose 6-phospha

7 on the extracytoplasmic domain of the bovine CD-MPR.

8 e roles of the Mr = 46,000 cation-dependent (CD-) MPR and the Mr = 300,000 cation-independent (CI-) M

9 controls for these cells, we also expressed CD-MPR trafficking mutants that either localize to the p

10 Mouse L cells stably expressing CD-MPRs with mutations that enhance GGA binding sorted c

11 its ligands is pH-dependent; the homodimeric CD-MPR binds lysosomal enzymes optimally in the pH envir

12 APP-overexpressing murine L cells with human CD-MPR.

13 sosomal hydrolases resulting from changes in CD-MPR expression affects amyloid precursor protein (APP

14 ta42 into the growth media nearly tripled in CD-MPR- and CD-MPRendo-expressing cells when compared wi

15 imilar to those reported for the full-length CD-MPR, demonstrating that the extracellular region of t

16 The two MPRs, the cation-dependent MPR (CD-MPR) and the insulin-like growth factor II/cation-ind

17 receptors (MPRs), the cation-dependent MPR (CD-MPR) and the insulin-like growth factor II/MPR (IGF-I

18 CI-MPR) and the 46 kDa cation-dependent MPR (CD-MPR) are key components of the lysosomal enzyme targe

19 CI-MPR) and the 46-kDa cation-dependent MPR (CD-MPR) are type I integral membrane glycoproteins that

20 Following metabolic labeling, mutant CD-MPRs were tested for their ability to bind pentamanno

21 Expression of CD-MPR resulted in a partial redistribution of a represe

22 In addition, saturating levels of CD-MPR resulted in the precipitation of only 50% of the

23 tion-dependent mannose 6-phosphate receptor (CD-MPR) and the insulin-like growth factor II/cation-ind

24 tion-dependent mannose 6-phosphate receptor (CD-MPR) contains a signal(s) that prevents the receptor

25 tion-dependent mannose 6-phosphate receptor (CD-MPR) encoding only the extracytoplasmic region, Stop1

26 tion-dependent mannose 6-phosphate receptor (CD-MPR) is a key component of the lysosomal enzyme targe

27 tion-dependent mannose 6-phosphate receptor (CD-MPR) plays a key role in the delivery of lysosomal en

28 tion-dependent mannose 6-phosphate receptor (CD-MPR), which is partially localized to early endosomes

29 with different concentrations of recombinant CD-MPR or soluble CI-MPR.

30 The CD-MPR bound weakly or undetectably to the phosphodieste

31 ncountered by the receptor including: 1) the CD-MPR bound at pH 6.5 (i.e. trans Golgi network) to a h

32 )Man(alpha1,2)Man-O-(CH(2))(8)COOMe), 2) the CD-MPR at pH 4.8 in an unbound state (i.e. endosome), an

33 an unbound state (i.e. endosome), and 3) the CD-MPR at pH 7.4 (i.e. cell surface).

34 aphic studies have shown that at pH 6.5, the CD-MPR bound to Man-6-P adopts a significantly different

35 fied as essential for Man-6-P binding by the CD-MPR and domains 1-3 and 9 of the CI-MPR.

36 ssential for carbohydrate recognition by the CD-MPR and domains 3 and 9 of the CI-MPR, but lacks two

37 Ligands precipitated by the CD-MPR appeared identical to those bound by the CI-MPR,

38 erences in binding affinity exhibited by the CD-MPR toward various lysosomal enzymes.

39 in lysosomal enzyme sorting mediated by the CD-MPR.

40 However, the CD-MPR binds the VHS domains more weakly than the CI-MPR

41 Mutation of these residues in the CD-MPR cytoplasmic tail to the corresponding residues in

42 zes a phenylalanine-tryptophan signal in the CD-MPR.

43 hospho-mono- or -diesters although, like the CD-MPR, it differentially recognized isomers of phosphor

44 not altered by overexpression of any of the CD-MPR constructs.

45 The extracytoplasmic domain of the CD-MPR crystallizes as a dimer, and each monomer folds i

46 s indicate that the endosomal sorting of the CD-MPR depends on the correct presentation of a diaromat

47 med the key role of Trp19 for sorting of the CD-MPR in endosomes, with Phe18, Phe13, and several neig

48 trating that the extracellular region of the CD-MPR is sufficient for high-affinity binding and that

49 ents mediated by increased expression of the CD-MPR may represent a potentially pathogenic mechanism

50 nd, but did not eliminate the ability of the CD-MPR to release ligand under acidic conditions.

51 The addition of the Phe18-Trp19 motif of the CD-MPR to the cytoplasmic tail of the lysosomal membrane

52 runcated glycosylation-deficient form of the CD-MPR, Asn81/Stop155, which has been modified to contai

53 urthermore, the C-terminal methionine of the CD-MPR, but not the C-terminal valine of the CI-MPR, inh

54 cids did not impair endosomal sorting of the CD-MPR, indicating that two aromatic residues located at

55 ions in the structure and functioning of the CD-MPR.

56 to the single extracytoplasmic domain of the CD-MPR.

57 y different quaternary conformation than the CD-MPR in a ligand-unbound state, a feature unique among

58 the total input ligands, suggesting that the CD-MPR binds a subpopulation of the Man-6-P glycoprotein

59 sCD-MPR, residues 1-154) have shown that the CD-MPR exists as a homodimer and exhibits two distinct c

60 tructurally similar to each other and to the CD-MPR and utilize a similar carbohydrate recognition me

61 omology to domains 3 and 9 as well as to the CD-MPR.

62 e modified GAAs demonstrate that, unlike the CD-MPR or domain 9 of the CI-MPR, domain 5 exhibits a 14

63 6-P-binding sites of the IGF-II/MPR with the CD-MPR implicates several residues of IGF-II/MPR domains

64 us mouse Abeta40 in L cells expressing these CD-MPR constructs but not overexpressing human APP.

65 cathepsin D more efficiently than wild-type CD-MPR.