ライフサイエンスコーパス: claudin-4

1 intermediate cell tight junction components (claudin-4).

2 s, such as zonula occludens-1, occludin, and claudin-4.

3 cells expressing CPE receptors claudin-3 and claudin-4.

4 h claudin-3, did not heterotypically bind to claudin-4.

5 ssion or distribution of ZO-1, claudin-1, or claudin-4.

6 itutively expressing wild-type claudin-3 and claudin-4.

7 s enterotoxin (cCPE) is a natural ligand for claudin-4.

8 situ along with a delay in up-regulation of claudin-4.

9 olymerization capacity between claudin-3 and claudin-4.

10 important roles in the regulatory network of Claudin-4.

11 claudin-7 and claudin-1 but not claudin-2 or claudin-4.

12 udin-2 chimera with a substituted ECL-2 from Claudin-4.

13 ng endogenous RNAs to affect the function of Claudin-4.

14 ick ascending limb of the loop of Henle; and claudin-4, -7, and -8 as determinants of collecting duct

15 ich correlated with the abundant presence of claudin-4, a known CPE receptor, in this villus region.

16 ingens enterotoxin, which is known to target Claudin-4, a matrix molecule highly expressed on mucosal

17 The expression of claudin-4, a protein involved in tight junction complexe

18 Here, we show that claudin-4, a prototypic barrier-forming claudin, reduces

19 laudin 2 expression at 6 hours and decreased claudin 4 and 7 expression at 24 hours; and iv) increase

20 reases in intestinal permeability, preserved claudin 4 and occludin localization at TJs, and decrease

21 EC and is associated with internalization of claudin 4 and occludin.

22 e 24 isoforms identified in mice and humans, claudin-4 and -3 serve as the receptor for Clostridium p

23 In LLC-PK1 cells, claudin-4 and -7 are powerful effectors of paracellular

24 he cation selectivity of the tight junction; claudin-4 and -7 function either as paracellular barrier

25 Fab) library to discover two sFabs that bind claudin-4 and cCpE complexes.

26 rier genes, including the IL-34 cytokine and claudins 4 and 8, and showed increased detection of key

27 carcinomas such as lipocalin 2, galectin 3, claudin 4, and cathepsin E.

28 essed by the alveolar epithelium, claudin-3, claudin-4, and claudin-18 are the most prominent; each c

29 permeable supports and expressed claudin-1, claudin-4, and claudin-8-key proteins for tight junction

30 nohistochemical analysis of ApoJ, claudin-3, claudin-4, and epithelial cellular adhesion molecule in

31 yses showed that the beta8 integrin subunit, claudin-4, and S100A1 provided the best distinction betw

32 ung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance o

33 In particular, claudin-3 and claudin-4 are frequently overexpressed in several neopla

34 However, claudin-3 and claudin-4 are the only family members capable of mediati

35 Rvp.1 (claudin-3) and CPE-R (claudin-4) are members of a larger family of transmembra

36 Using acGFP-claudin 4 as a biosensor of TJ remodeling, we observed i

37 have also implicated certain claudins (e.g., Claudin-4) as receptors for Clostridium perfringens ente

38 es some claudin tight junction proteins (eg, claudin-4) as receptors to form Ca2+-permeable pores in

39 s zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction protei

40 of non-junctional claudin molecules such as claudin-4 at apical membranes.

41 t junction proteins occludin, claudin-1, and claudin-4, at mRNA and protein levels.

42 f receptors in this villus region, and (iii) claudin-4 being an important intestinal receptor for CPE

43 tions with previous studies suggest that the claudin-4 binding site is on a large surface loop betwee

44 Decreased claudin-4, caudin-7, and E-cadherin expression in Lpa1(-

45 determined structures of each sFab bound to claudin-4-cCpE complexes using cryo-EM.

46 Rat fibroblast transfectants expressing a Claudin-4 chimera, where the natural ECL-2 was replaced

47 In contrast, claudin-4 chimeras containing either the first EL domain

48 other tight junctional proteins (claudin-3, claudin-4, claudin-5, occludin, and ZO-1) and adherent j

49 transcription factor, as well as E-cadherin, claudin 4 (Cldn4), and the small GTPase Rab25.

50 Claudin-3 (CLDN3) and claudin-4 (CLDN4) are the major structural molecules tha

51 Gene expression experiments identified claudin-4 (CLDN4) as a key tight junction protein dysreg

52 ponse to hypertonicity, the up-regulation of claudin-4 (Cldn4) expression, and not other claudins, wa

53 egrin subunit, bone morphogenetic protein-7, claudin-4, collagen type IX alpha2, cellular retinoic ac

54 Claudin-4 concentrations are known to increase during lu

55 To define the structural constraints for the claudin-4/Cpe30 interaction, a surface plasmon resonance

56 Immunohistochemical validation revealed that claudin 4, CXCR4, S100A4, and mesothelin were expressed

57 increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice.

58 We identified a novel claudin-4-driven mechanism that promotes immune evasion

59 ugh a mechanism involving its recruitment of claudin-4 during TJ assembly.

60 also observed using either rclaudin-4 or the claudin-4 ECL-2 peptide in both a preincubation assay an

61 reincubation or coincubation of CPE with the claudin-4 ECL-2 peptide significantly and specifically i

62 However, the claudin-4 ECL-2 peptide was unable to neutralize cytotox

63 These results suggest that claudin-4 ECL-2 peptides should be further investigated

64 her a synthetic peptide corresponding to the claudin-4 ECL-2 sequence can similarly inhibit CPE actio

65 Claudin-4 exchange is not affected.

66 clearance and demonstrate that the amount of claudin-4 expressed may provide specific information reg

67 BALB/neuT mice, which spontaneously develop claudin-4-expressing breast cancer lesions.

68 d cCPE.GST for claudin-4 was confirmed using claudin-4-expressing MDA-MB-468 and SQ20b cells, compare

69 Dual targeting of claudin-4-expressing tumors with CMP and niraparib resha

70 Taken together, (111)In-cCPE.GST targets claudin-4 expression in frank tumors and preneoplastic t

71 (siRNA)-mediated knockdown of claudin-3 and claudin-4 expression in ovarian cancer cell lines reduce

72 Claudin-4 expression increases ~16 fold in cancer as com

73 regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, whic

74 for known targets, including ROCK and ezrin, claudin-4 expression, and barrier permeability.

75 cancer cells, correlating with claudin-3 and claudin-4 expression.

76 genous RNAs (ceRNAs), resulting in increased claudin-4 expression.

77 nsor of TJ remodeling, we observed increased claudin 4 fluorescence recovery after photobleaching (FR

78 g CPE with soluble recombinant Claudin-4, or Claudin-4 fragments containing ECL-2 specifically blocke

79 ular chloride channel, and delocalization of claudin-4 from the tight junction.

80 that in mouse kidney collecting duct cells, claudin-4 functioned as a Cl(-) channel.

81 n tumors were found to express claudin-3 and claudin-4 genes at significantly higher levels when comp

82 and others have recently found claudin-3 and claudin-4 genes to be highly expressed in ovarian cancer

83 tor alpha increased the proportion of mobile claudin 4 in the TJ.

84 Immunodetection of the TJ protein claudin 4 in WT and mMCP5-deficient mice indicated a sig

85 low or undetectable levels of claudin-3 and claudin-4 in all regions tested by Western and immunohis

86 the level of expression of claudin-3 and/or claudin-4 in chemotherapy-naive and chemotherapy-resista

87 We report the structure of human claudin-4 in complex with cCpE, which reveals that enter

88 llular ionic selectivity, we expressed human claudin-4 in cultured MDCK cells using an inducible prom

89 this study, we discover a network regulating Claudin-4 in gastric cancer.

90 ned to study the expression of claudin-3 and claudin-4 in human prostate tissue as potential targets

91 In particular, a protective role for claudin-4 in preventing lung injury has emerged.

92 Claudin-4-induced loss of claudin channel function is ac

93 nce correlated directly with the kinetics of claudin-4 induction.

94 Together, our data show that claudin-4 interacts with claudin-8 and that their associ

95 dextran transmucosal flux); ii) occludin and claudin 4 internalization at 12 hours (as assessed by im

96 n the collecting duct cells, the assembly of claudin-4 into TJ strands required its interaction with

97 patocytes, claudin 3 is uniformly expressed, claudin 4 is absent, and claudin 5 is only expressed in

98 Claudin-4 is overexpressed in several premalignant precu

99 Because claudin-4 is overexpressed on some human cancers, the to

100 The second extracellular loop (Ecl2) of claudin-4 is responsible for the binding to the C-termin

101 We observe that Claudin-4 is up-regulated in gastric cancer and is assoc

102 In particular, CLDN4 (encoding claudin-4) is overexpressed in ovarian cancer.

103 es, and the TJ proteins occludin, claudin-1, claudin-4, junctional adhesion molecule, and ZO-1.

104 Claudin-4 knockout or overexpression has minimal effects

105 associated with alveolar fluid clearance or claudin-4 levels.

106 These data suggest that claudin-4 may promote alveolar fluid clearance and demon

107 Transfectants expressing a Claudin-4(N149D) mutant lost the ability to bind or resp

108 ng MDA-MB-468 and SQ20b cells, compared with claudin-4-negative HT1080 cells.

109 significantly higher than in (111)In-GST or claudin-4-negative HT1080 tumors (6.72 +/- 0.18 vs. 3.88

110 junction-deficient epithelial cells, mutated claudin-4 not only influences tight junction morphology

111 els of E-cadherin, desmoplakin, plakoglobin, claudin-4, occludin, zonula occludens 1, and tricellulin

112 Claudin-4, often overexpressed in HGSC, is strongly link

113 Whereas the short peptides bound native claudin-4 on transfected CHO cells in pull-down assays,

114 Knockdown of claudin-4 or -7 expression depressed the permeation of C

115 Loss of claudin-4 or -7 expression elevated the permeation of Na

116 , preincubating CPE with soluble recombinant Claudin-4, or Claudin-4 fragments containing ECL-2 speci

117 Our data show that claudin-4 orchestrates tumor immune evasion and survival

118 d in vitro ovarian cancer models with stable claudin-4 overexpression and knockdown.

119 Mammary fat pads in mice aged 80 d bore claudin-4-positive aplastic lesions and accumulated (111

120 The uptake of (111)In-cCPE.GST in claudin-4-positive MDA-MB-468 xenograft tumors in athymi

121 Overt mammary tumors were claudin-4-positive, and (111)In-cCPE.GST uptake was 3.2

122 Up-regulation of claudin 4 protein rescued these mobility defects and cyt

123 ous studies have revealed that claudin-3 and claudin-4 proteins are highly overexpressed in ovarian c

124 rotoxin with soluble full-length recombinant claudin-4 (rclaudin-4), which is a CPE receptor, but not

125 with the downstream transmembrane domain of claudin-4 reconstituted the basic structural requirement

126 Claudin-4 regulated type I interferon signaling through

127 Claudin-4 reinforce proliferation, invasion, and EMT in

128 GST fusions with claudin-4 revealed that Ecl2 with the downstream transme

129 ified by us (CD44, CD24, EpCAM, aquaporin 5, claudin-4, secretin receptor, claudin-7, V-ros sarcoma v

130 However, claudin-4 selectively inhibits flux across cation channe

131 uction of these residues from claudin-3 into claudin-4 significantly enhances polymerization in nonep

132 uding p53, HER2/neu, IL-6, kallikrein 6, and claudin-4, some of which may be susceptible to molecular

133 Claudin-4 staining demonstrated a positive correlation w

134 Claudin-4 staining was lower in lungs from donors with g

135 relation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with hist

136 disruption of the claudin-8 interaction with claudin-4, the paracellular chloride channel, and deloca

137 t Asn(44) to the corresponding amino acid in claudin-4 (Thr) produced a claudin capable of heterotypi

138 claudin 2, a highly restricted expression of claudin 4 to colonic surface cells, and the finding that

139 binding of claudin-1 and claudin-2, but not claudin-4, to S408A occludin tail is increased relative

140 r peptides selected by phage display against claudin-4-transfected CHO cells and a 12-mer Cpe mutant

141 In contrast, expression of claudin-3 and claudin-4 was absent in adjacent normal brain tissue.

142 overexpressed epithelial monolayers and that claudin-4 was also restricted from intercellular contact

143 The affinity of radiolabeled cCPE.GST for claudin-4 was confirmed using claudin-4-expressing MDA-M

144 ely charged lysine residue at position 65 of claudin-4 was critical for its anion selectivity.

145 Claudin-4 was localized to Triton X-100-soluble gradient

146 ferentially isolated as a homodimer, whereas claudin-4 was monomeric.

147 Claudin-4 was observed to interact with claudin-8 using

148 blot analysis, mRNAs for both claudin-3 and claudin-4 were expressed at high levels in prostate tiss

149 immunohistochemical analysis, claudin-3 and claudin-4 were expressed frequently in metastases from b

150 We found that although claudin-3 and claudin-4 were heteromerically compatible when expressed

151 Importantly, Cpe30 retained its binding to claudin-4 when fused to the C terminus of influenza hema

152 Analyses in nonepithelial cells show that claudin-4, which is incapable of independent polymerizat

153 a claudin capable of heterotypic binding to claudin-4 while still retaining the ability to bind to c

154 d (residues 194-319) binds to purified human claudin-4 with a 1:1 stoichiometry and affinity in the s

155 de-based molecular imaging agent targeted to claudin-4 with accumulation to ~25% injected activity pe

156 peptide also showed significant affinity for claudin-4 with this SPR assay, suggesting that a short p

157 tly, whereas no obvious change of claudin-1, claudin-4, zonula occludens protein 1, and zonula occlud