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 CI-MPR is multifunctional and modulates embryonic growth

3 ary, we found that tPA contains M6P and is a CI-MPR ligand.

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

5 Among CI-MPR functions is the delivery of acid hydrolases to l

6 that AP-1gamma2 is dispensable for ATP7B and CI-MPR exit from the TGN while being critically required

7 hile being critically required for ATP7B and CI-MPR retrieval from endosomes to the TGN.

8 overed that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) do

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

10 rms membranes with bis-phosphoinositides and CI-MPR cargo but surprisingly does not recruit Retromer.

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

12 contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner.

13 This study shows that both CI-MPR and ATP7B interact with a variant of the clathrin

14 the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities.

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

16 lasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen a

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

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

19 letion leads to the retention of endocytosed CI-MPR in endosomes enriched in retromer complex subunit

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

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

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

23 2, forming a multimeric complex required for CI-MPR sorting.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

40 by inducing global conformational changes of CI-MPR.

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

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

43 revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interac

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

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

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

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

48 Precise subcellular localization of CI-MPR and ATP7B is essential for the proper functioning

49 in the sorting and trafficking machinery of CI-MPR and ATP7B, highlighting its essential role in the

50 The extracellular region of CI-MPR comprises 15 homologous domains with binding site

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

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

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

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

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

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

57 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolase

58 on-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R

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

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

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

62 on-Independent Mannose-6-phosphate receptor (CI-MPR) and the ATP7B copper transporter.

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

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

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

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

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

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

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

70 on-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of pa

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

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

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

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

75 on-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme tra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

100 We discovered that rhSGSH utilizes both the CI-MPR and LRP1 receptors for uptake into patient fibrob

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

135 dosomal organization and distribution of the CI-MPR.

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

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

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

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

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

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

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

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

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

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

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

147 sminogen activator (tPA), also interact with CI-MPR.

148 eports that phosphorylated gD interacts with CI-MPR.