ライフサイエンスコーパス: CI-MPR

1 CI-MPR cytoplasmic domain residues 1-47 are dispensable,

2 erexpressing cells were fractionated using a CI-MPR affinity column, 35-45% of the total LIF molecule

3 CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5

4 ndent mannose 6-phosphate receptors (CD- and CI-MPRs) bind the phosphomannosyl recognition marker of

5 MPR containing the ecto-domain of the bovine CI-MPR and the murine transmembrane and cytoplasmic doma

6 analysis revealed that internalized chimeric CI-MPR overlaps almost completely with the endogenous CI

7 ression of sequences antisense to the cloned CI-MPR gene induced apoptosis by themselves.

8 erlaps almost completely with the endogenous CI-MPR but only partially with individual markers for th

9 In summary, beta2-agonist treatment enhanced CI-MPR-mediated uptake and trafficking of GAA in mice wi

10 Finally, CI-MPR-KO/GAA-KO mice did not respond to combination the

11 2, forming a multimeric complex required for CI-MPR sorting.

12 es GGA3 phosphorylation, releasing GGA3 from CI-MPR and early endosomes.

13 gf2r/Igf2 double mutants, mice lacking IGF2R/CI-MPR and CD-MPR survive in an IGF-II null background a

14 receptor (IGF1R), the type 2 receptor (IGF2R/CI-MPR) serves IGF-II turnover.

15 pendent mannose 6-phosphate receptor (IGF-II/CI-MPR).

16 AR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport.

17 in this study reappraise retromer's role in CI-MPR transport.

18 iously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-alpha-g

19 the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline.

20 adjunctive beta2-agonist treatment increased CI-MPR expression and enhanced efficacy from gene therap

21 aluated beta2-agonist drugs, which increased CI-MPR expression in GAA knockout (KO) mice.

22 MPR and the Mr = 300,000 cation-independent (CI-) MPR in lysosomal targeting, an assay has been devel

23 from clenbuterol in GAA-KO mice that lacked CI-MPR in muscle, where it failed to reverse the high gl

24 ascade controlling PACS-1- and GGA3-mediated CI-MPR sorting.

25 ent retrieval of the cation-independent MPR (CI-MPR).

26 t contains LAMP-1, LAMP-2, and NPC1, but not CI-MPR, similar to the cholesterol-rich compartment in N

27 he addition of clenbuterol in the absence of CI-MPR, as was lysosomal vacuolation, which correlated w

28 Saturating concentrations of CI-MPR resulted in the complete recovery of each Man-6-P

29 Cycling of CI-MPR between the TGN and early endosomes is mediated b

30 ocked apoptosis induced by the expression of CI-MPR antisense sequences.

31 Clenbuterol, which increases expression of CI-MPR in muscle, was administered with the AAV vector.

32 of IncE peptide inhibits the interaction of CI-MPR with SNX5.

33 activity, as measured by decreased levels of CI-MPR and lower activities of cellular lysosomal hydrol

34 The integral role of CI-MPR was demonstrated by the lack of effectiveness fro

35 nts that mediate the retrograde transport of CI-MPR from endosomes to the TGN independently of the co

36 cating that clenbuterol's effect depended on CI-MPR expression.

37 teps, GGA3 and PACS-1 bind to an overlapping CI-MPR trafficking motif and their sorting activity is c

38 own or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked s

39 ient for a high-affinity binding to receptor CI-MPR, while the presence of a M6P moiety at the alpha-

40 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolase

41 on-independent mannose-6-phosphate receptor (CI-MPR) and sortilin.

42 on-independent mannose 6-phosphate receptor (CI-MPR) and the 46 kDa cation-dependent MPR (CD-MPR) are

43 on-independent mannose 6-phosphate receptor (CI-MPR) and the 46-kDa cation-dependent MPR (CD-MPR) are

44 on-independent mannose 6-phosphate receptor (CI-MPR) block apoptosis induced by either gD(-/-) or gD(

45 on-independent mannose-6-phosphate receptor (CI-MPR) follows a highly regulated sorting itinerary to

46 on-independent mannose 6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN),

47 on-independent mannose 6-phosphate receptor (CI-MPR) from its normal perinuclear localization to larg

48 on-independent mannose 6-phosphate receptor (CI-MPR) has been well studied, its intracellular itinera

49 on-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle.

50 on-independent mannose 6-phosphate receptor (CI-MPR) is a multifunctional protein that binds diverse

51 on-independent mannose-6-phosphate receptor (CI-MPR) mediated uptake.

52 on-independent mannose 6-phosphate receptor (CI-MPR) mediates sorting of lysosomal hydrolase precurso

53 on-independent mannose 6-phosphate receptor (CI-MPR) mediates the intracellular transport of newly sy

54 on-independent mannose 6-phosphate receptor (CI-MPR) plays a critical role in the trafficking of newl

55 on-independent mannose-6-phosphate receptor (CI-MPR), a receptor for lysosomal hydrolases, and other

56 on-independent mannose 6-phosphate receptor (CI-MPR), and we analyzed the effects of this modificatio

57 on-independent mannose 6-phosphate receptor (CI-MPR), which contains multiple mannose 6-phosphate (Ma

58 on-independent mannose 6-phosphate receptor (CI-MPR)-mediated endocytosis of the enzyme by the affect

59 on-independent mannose-6-phosphate receptor (CI-MPR)-mediated uptake and intracellular trafficking of

60 on-independent mannose 6-phosphate receptor (CI-MPR).

61 on-independent mannose 6-phosphate receptor (CI-MPR).

62 on-independent mannose-6-phosphate receptor (CI-MPR).

63 nd -dependent mannose 6-phosphate receptors (CI-MPR and CD-MPR) for high mannose-type N-glycans of de

64 n-independent mannose-6-phosphate receptors (CI-MPR) in the soma is disrupted in mutant hAPP neurons,

65 s highly conformation dependent and requires CI-MPR residues that are proximal to the membrane.

66 that TIP47 interaction with the 163-residue CI-MPR cytoplasmic domain is highly conformation depende

67 SH did regulate retromer-mediated retrograde CI-MPR trafficking, which required its association with

68 achomatis infection interferes with the SNX5:CI-MPR interaction, suggesting that IncE and CI-MPR are

69 centrations of recombinant CD-MPR or soluble CI-MPR.

70 Newly synthesized CI-MPR and cathepsin D were shown to traverse through an

71 These data demonstrate that CI-MPR takes a complex route that involves multiple sort

72 These results suggest that CI-MPR-mediated endocytosis of rhGAA is an important pat

73 The CI-MPR also recognizes lysosomal enzymes that elude UCE

74 The CI-MPR is a receptor for plasminogen, and this interacti

75 The CI-MPR recognizes lysosomal enzymes bearing the Man-6-P

76 unique carbohydrate binding sites allows the CI-MPR to interact with the structurally diverse phospho

77 kringles 1-4, but not kringles 1-3, bind the CI-MPR, indicating an essential role for the LBS in krin

78 tion to its role in lysosome biogenesis, the CI-MPR interacts with a number of different extracellula

79 MPR appeared identical to those bound by the CI-MPR, with apparent affinity constants ranging between

80 on of the Man-6-P glycoproteins bound by the CI-MPR.

81 By contrast, the CI-MPR bound with high affinity to glycans containing ei

82 is critical to achieve high affinity for the CI-MPR receptor.

83 GAA containing high affinity ligands for the CI-MPR represents a strategy by which the potency of rhG

84 To determine how the CI-MPR recognizes phosphodiesters, the structure of doma

85 ic tail to the corresponding residues in the CI-MPR conferred either full binding (H63D mutant), inte

86 encoding the N-terminal three domains of the CI-MPR (Dom1-3His) which contains both a mannose 6-phosp

87 our alanines to the C-terminal valine of the CI-MPR also severely reduced GGA binding, demonstrating

88 were performed using truncated forms of the CI-MPR and plasminogen.

89 the loop connecting domains 1 and 2) of the CI-MPR are key determinants for plasminogen binding but

90 ucture of the N-terminal 432 residues of the CI-MPR at 1.8 A resolution, which encompass three out of

91 sults show that the N-terminal region of the CI-MPR containing domains 1 and 2, but not domain 1 alon

92 state localization of a chimeric form of the CI-MPR containing the ecto-domain of the bovine CI-MPR a

93 The extracytoplasmic region of the CI-MPR contains 15 contiguous domains, and the two high

94 ts with the membrane-proximal portion of the CI-MPR cytoplasmic domain.

95 dition, expression of truncated forms of the CI-MPR demonstrated that domain 9 can be expressed as an

96 Domain 5 of the CI-MPR exhibits significant sequence homology to domains

97 The extracellular region of the CI-MPR is comprised of 15 repetitive domains and contain

98 of the entire extracytoplasmic region of the CI-MPR that provides a context with which to envision th

99 To identify the lysine residue(s) of the CI-MPR that serve(s) as an essential determinant for rec

100 o high-affinity Man-6-P binding sites of the CI-MPR to domains 1-3 and 9 and one low-affinity site to

101 e that retromer prevents the delivery of the CI-MPR to lysosomes, probably by sequestration into endo

102 This ability of the CI-MPR to target phosphodiester-containing enzymes ensur

103 the three carbohydrate binding sites of the CI-MPR, a phosphorylated glycan microarray was probed wi

104 ion by the CD-MPR and domains 3 and 9 of the CI-MPR, but lacks two cysteine residues predicted to for

105 -Golgi transport, mediating retrieval of the CI-MPR, but not furin.

106 ence increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolase

107 e that, unlike the CD-MPR or domain 9 of the CI-MPR, domain 5 exhibits a 14-18-fold higher affinity f

108 ucture of the N-terminal 432 residues of the CI-MPR, encompassing domains 1-3, was solved in the pres

109 CD-MPR, but not the C-terminal valine of the CI-MPR, inhibited GGA binding.

110 array was probed with truncated forms of the CI-MPR.

111 g by the CD-MPR and domains 1-3 and 9 of the CI-MPR.

112 r interacts with the cytosolic domain of the CI-MPR.

113 dosomal organization and distribution of the CI-MPR.

114 nalysis of LIF glycopeptides enriched on the CI-MPR column revealed that all six N-glycan sites could

115 lacking mammalian VPS26 fail to retrieve the CI-MPR, resulting in either rapid degradation of or misl

116 R binds the VHS domains more weakly than the CI-MPR.

117 together, these results demonstrate that the CI-MPR contains a third Man-6-P recognition site that is

118 Thus, GGA2 binding to the CI-MPR is important for lysosomal enzyme targeting.

119 From validating the CI-MPR dependency of SNX1/2-SNX5/6 tubular profile forma

120 hese results show the mechanism by which the CI-MPR recognizes Man-P-GlcNAc-containing ligands and pr

121 ablish that SNX5 and SNX6 associate with the CI-MPR through recognition of a specific WLM endosome-to

122 rovide an initial structural basis for TIP47-CI-MPR association.

123 CS-1Ser(278), promoting binding of PACS-1 to CI-MPR to retrieve the receptor to the TGN.

124 into the endosomal compartment by binding to CI-MPR.

125 eports that phosphorylated gD interacts with CI-MPR.