ライフサイエンスコーパス: megalin

1 toxicity, entering the cell via the receptor megalin.

2 d hormones is encountered in animals lacking megalin.

3 ibodies from rats with AHN induced by native megalin.

4 ional or other structural features of native megalin.

5 pitation assays, GST-GIPC specifically binds megalin.

6 DSDV motif found at the carboxyl-terminus of megalin.

7 he apolipoprotein E receptor-2 (apoER2), and megalin.

8 proximal tubule epithelia which also express megalin.

9 esicles most of the NHE3 coprecipitated with megalin.

10 DL-R), apolipoprotein E receptor 2, LRP, and megalin.

11 ipitation of 125I-Tg with antibodies against megalin.

12 cortical membranes, Lp B-70.5 bound only to megalin.

13 d and immunoblotted the same protein, namely megalin.

14 that Tg endocytosis is partially mediated by megalin.

15 id cell line, can bind and endocytose Tg via megalin.

16 port of vitamin B12: role of TCblR/CD320 and megalin.

17 cidin staining in proximal tubules that lack megalin.

18 e renal proximal tubule by another receptor, megalin.

19 two LDL receptor-related proteins: LRP1 and Megalin.

20 ytic adaptor AP-2 prevents fast recycling of megalin.

21 ves the expression of the endocytic receptor megalin.

22 membrane proteolysis (RIP) and expression of megalin.

23 )/rs2075252(TT)/rs4668123(T-)] compared with Megalin(1) [rs3755166(-)/rs2075252(CC)/rs4668123(-)] was

24 The Megalin(1) SNPHAP (GCC) was related to greater decline a

25 SNP latent classes as predictors for LARCCs, Megalin(2) [rs3755166(-)/rs2075252(TT)/rs4668123(T-)] co

26 In women, the Megalin(2) SNPHAP (ACC) was associated with slower decli

27 , is induced by immunization with autologous megalin, a 600-kDa cell surface glycoprotein isolated fr

28 onated by SDS-PAGE revealed that Sepp1 binds megalin, a lipoprotein receptor localized to the proxima

29 rolemia (ARH) is required for trafficking of megalin, a member of the LDL receptor family, from EE to

30 uptake of lipophilic vitamins and hormones, megalin, a member of the LDL receptor gene family, regul

31 Megalin, a member of the low density lipoprotein recepto

32 LRP2 encodes megalin, a multiligand uptake receptor that regulates le

33 inuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption

34 Analysis of megalin, a prototypical GIPC/synectin-binding receptor,

35 tion of several endocytic markers, including megalin, a receptor for nutrients and proteins; ARH, a c

36 Suppression of megalin activity or expression by treatment with either

37 or megalin, we explored the possibility that megalin acts in conjunction with cubilin to mediate HDL

38 These data demonstrate that megalin acts together with cubilin to mediate HDL endocy

39 facilitates endocytosis of megalin, escorts megalin along its endocytic route and raise the possibil

40 munofluorescence, ANKRA is concentrated near megalin along the plasma membrane of L2 cells and in the

41 rl morpholino showed truncated expression of megalin along the pronephric kidney, consistent with a s

42 recipitation experiments confirmed that anti-megalin and anti-DPPIV antibodies co-precipitate differe

43 33(+) cells express proximal tubular markers megalin and aquaporin-1.

44 codazole, the recycling endosomes containing megalin and ARH disperse.

45 teady state, apical TC-R was associated with megalin and both these proteins were enriched in an intr

46 Megalin and cubilin are cooperating receptors essential

47 lbumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface

48 DFO treatment, with concomitantly decreased megalin and cubilin expression levels and increased TfR1

49 Megalin and cubilin levels detected by immunochemilumine

50 Working in concert with megalin and cubilin, a nonselective multireceptor comple

51 Receptor-mediated endocytosis, involving megalin and cubilin, mediates renal proximal-tubular rea

52 LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal

53 Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proxim

54 expression of the main scavenger receptors, MEGALIN and CUBILIN.

55 e proximal tubule (PT) multiligand receptors megalin and cubilin.

56 an's r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected pl

57 oblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman's r

58 istribution of cell surface proteins such as megalin and E-cadherin and propose that loss of polarity

59 nsional model describing the complex between megalin and gentamicin.

60 of the 10th complement type repeat of human megalin and investigated its interaction with gentamicin

61 We studied abundance of megalin and its intracellular adaptor protein Dab2 by im

62 ary for gamma-secretase mediated cleavage of megalin and release of a tail fragment that mediates tra

63 roteins that bind to the cytoplasmic tail of megalin, and a protein fragment from a mouse embryonic c

64 ls that ANKRA is more broadly expressed than megalin, and by immunofluorescence ANKRA is also express

65 ors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-feta

66 ANKRA2 is a megalin- and BKCa potassium channel-interacting factor,

67 ivity or expression by treatment with either megalin antibodies or megalin antisense oligodeoxynucleo

68 z. anti-receptor-associated protein and anti-megalin antibodies.

69 Furthermore, megalin antisense oligodeoxynucleotide treatment resulte

70 treatment with either megalin antibodies or megalin antisense oligodeoxynucleotides resulted in inhi

71 e reactive in Western blots with rabbit anti-megalin antiserum, whereas the insect cell-derived prote

72 the Tg released by heparin had been bound to megalin ( approximately 60-80%).

73 On internalization of megalin, ARH and megalin are first seen in clathrin coated pits followed

74 On internalization of megalin, ARH and megalin are first seen in clathrin coat

75 ce screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport.

76 Furthermore, they implicate megalin as a new regulatory component of the Shh signali

77 er isoform NHE3 exists as both 9.6 and 21 S (megalin-associated) oligomers in the renal brush border.

78 ctive form present in microvilli and a 21 S, megalin-associated, inactive form in the intermicrovilla

79 culovirus construct elicited high titer anti-megalin autoantibodies and developed glomerular immune d

80 entially in Western blot and ELISA with anti-megalin autoantibodies from rats with AHN induced by nat

81 lymph node cells and induced high-titer anti-megalin autoantibodies in Lewis rats.

82 ermore, the 210-kDa Tg polypeptide inhibited megalin binding to intact Tg by approximately 70%.

83 f rat Tg and have studied its involvement in megalin binding.

84 taining the peptide sequence is required for megalin binding.

85 rbent assays and ligand blot binding assays, megalin bound to intact Tg (660 and 330 kDa) and, to a e

86 Megalin-bound Tg was releasable by heparin.

87 ANKRA interacts with megalin but not with low-density lipoprotein receptor re

88 of LDL can bind to both the LDL receptor and megalin, but the molecular interactions of apo B-100 wit

89 ptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry.

90 ncreased, suggesting that Tg internalized by megalin bypassed the lysosomal pathway, possibly with re

91 MDCK cells disrupted apical localization of megalin, causing its redistribution to the basolateral m

92 of the brush border target antigen excluded megalin, CD10, and maltase.

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

94 A striking deficiency of urinary megalin, compared with normal individuals (n = 42), was

95 The amount recovered was markedly reduced by megalin competitors, indicating that megalin mediates Tg

96 t assay (ELISA), was markedly reduced by two megalin competitors, receptor-associated protein (RAP) a

97 ls were incubated with Tg plus either of two megalin competitors, T3 release was increased, suggestin

98 the amount released was markedly reduced by megalin competitors.

99 teracting proteins in the cubilin-amnionless-megalin complex that are involved in the maternal-fetal

100 In contrast to the previously described NHE3-megalin complex, which principally resides in a dense me

101 The cytoplasmic domain of megalin contains amino acid motifs that have the potenti

102 The cytoplasmic tail of megalin contains two FXNPXY motifs.

103 , the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of ren

104 encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as e

105 e revealed progressive loss of expression of megalin, cubilin, sodium-glucose cotransporter 2, and ty

106 ramatically increased internalization of the megalin-cubilin ligand albumin as well as the fluid phas

107 Although the role of the megalin-cubilin receptor complex (MCRC) in this process

108 ME) through the multiligand receptor complex megalin-cubilin.

109 mice, correlating with a reduction in renal megalin/cubilin expression in knockout mice to about 10%

110 protein alpha1-microglobulin, an established megalin/cubilin ligand.

111 (99m)Tc-DMSA is thus critically dependent on megalin/cubilin receptor function and therefore is a mar

112 ide gel electrophoresis demonstrated that in megalin/cubilin-deficient mice an increased amount of (9

113 We have used megalin/cubilin-deficient mice produced by gene knockout

114 The reduced renal uptake in megalin/cubilin-deficient mice was accompanied by an inc

115 Control or megalin/cubilin-deficient mice were injected intravenous

116 In megalin/cubilin-deficient mice, we observed decreased up

117 99m)Tc-DMSA was identified in scintigrams of megalin/cubilin-deficient mice.

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

119 l tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion o

120 Hence, Megalin defines the apical recycling pathway of epitheli

121 idin is reaborbed in the proximal tubules by megalin dependent endocytosis.

122 ce of gentamicin, a competitive inhibitor of megalin-dependent endocytosis.

123 ltered by the kidney but can bypass sites of megalin-dependent recapture, resulting in urinary excret

124 kidney selenium homeostasis is mediated by a megalin-dependent Sepp1 uptake pathway in the proximal t

125 While megalin did not bind to HDL, delipidated HDL, or apoA-I,

126 h the tail of LRP, the tails of the LDLR and megalin display significantly lower levels of endocytosi

127 TC-R expressed in apical BBM complexes with megalin during its transcytosis from the BLM.

128 Megalin enters polarized MDCK cells through segregated a

129 lts show that ARH facilitates endocytosis of megalin, escorts megalin along its endocytic route and r

130 nic hedgehog (Shh) or the endocytic receptor megalin exhibit common neurodevelopmental abnormalities.

131 Cubilin and megalin exhibited coincident patterns of mRNA expression

132 l Sp1 sites in the nuclear extracts of gp600/megalin expressing cell lines.

133 rush border region of PTE and are present in megalin-expressing cell lines.

134 Megalin-expressing cells internalized N-Shh through a me

135 This was correlated with an increase in megalin expression (P < 0.05 for diabetic vs. treated) a

136 Leptin significantly stimulated megalin expression 2.1-fold in lo-Meg cells (P < 0.01).

137 Megalin expression at the luminal membrane is reduced by

138 This was associated with increased megalin expression on thyrocytes and increased serum Tg

139 Megalin expression remained unaltered in adult WT and KO

140 Megalin expression was about the same in both WT and KO

141 Similarly, proximal tubule megalin expression was reduced by diabetes but was prese

142 In hMSCs with high constitutive megalin expression, both 1alpha,25(OH)(2)D(3) and 25(OH)

143 repeat are necessary for activation of gp600/megalin expression.

144 was associated with preservation of cortical megalin expression.

145 understand the mechanisms that control gp600/megalin gene expression, we cloned and functionally char

146 characterization of the regulation of gp600/megalin gene is likely to advance the knowledge of the r

147 Vitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cogni

148 Sex-specific VDR and Megalin gene variations can modify age-related cognitive

149 gment of the 5'-flanking region of rat gp600/megalin gene.

150 equires recycling of the endocytic receptors megalin (gp330) and cubilin.

151 Here we show that megalin (gp330), a Tg receptor on thyroid cells, plays a

152 We recently reported that megalin (gp330), an endocytic receptor found on the apic

153 le in a manner similar to that described for megalin (gp330).

154 bits binding of Tg to its endocytic receptor megalin (gp330).

155 Megalin (gp330, LRP-2) is a protein structurally related

156 reduced transport by a lipoprotein receptor, megalin/gp330, in the proximal tubule.

157 membrane endocytic receptor glycoprotein 330/megalin (hereafter referred to as megalin) is localized

158 The megalin homologue LRP-1 is essential for growth and deve

159 Proteins were blotted and probed with anti-megalin IgG, anti-cubilin IgG, or receptor-associated pr

160 d AP-1 silencing disrupted apical sorting of megalin in both biosynthetic and recycling routes.

161 n, these signaling molecules cosediment with megalin in brush border and microvillar fractions.

162 ARH colocalizes with megalin in clathrin coated pits and in recycling endosom

163 ncentration of Galphai3, GIPC, and GAIP with megalin in endocytic compartments of the proximal tubule

164 ol and associated with membranes enriched in megalin in L2 cells and proximal tubule cells.

165 ly described the apical recycling pathway of megalin in Madin-Darby canine kidney (MDCK) cells and fo

166 e evaluated the role of TC, TCblR/CD320, and megalin in maternofetal transport of B12 in a TCblR/CD32

167 idin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type

168 of NHE3 exists as a multimeric complex with megalin in the brush border of the proximal tubule.

169 fraction of the transporter colocalized with megalin in the intermicrovillar region of the brush bord

170 nd specifically with the cytoplasmic tail of megalin in the yeast two-hybrid system and glutathione-S

171 ARH also binds to the first FXNPXY motif of megalin in two-hybrid, pull-down and coimmunoprecipitati

172 med the in vivo co-localization of Sepp1 and megalin in wild type kidneys and demonstrated the absenc

173 -containing vesicles, which colocalized with megalin, in podocin-positive cells.

174 n (RAP) and 1H2 (monoclonal antibody against megalin), indicating that much of the Tg released by hep

175 Immunization with megalin induces active Heymann nephritis, which reproduc

176 Models for megalin interaction(s) with Sonic Hedgehog (Shh) have be

177 embranes, indicating specificity of the NHE3-megalin interaction.

178 ryogenesis is well established; how and when megalin interacts with Shh is becoming a pertinent quest

179 The ability of megalin-internalized N-Shh to bypass lysosomes may relat

180 Megalin is a complex immunological target with four disc

181 We show that, like TfR, Megalin is a long-lived and fast-recycling receptor.

182 Megalin is a member of the low-density lipoprotein recep

183 Megalin is a transmembrane protein involved in clathrin-

184 Megalin is a transmembrane receptor for serum d-binding

185 Megalin is also expressed in lung, eye, intestine, uteru

186 Together, these findings show that megalin is an efficient endocytic receptor for N-Shh.

187 Gp600/megalin is an endocytic receptor belonging to the low-de

188 Megalin is an endocytic receptor that binds multiple lig

189 ed in the visceral yolk sac of KO mice where megalin is expressed and provides an alternate mechanism

190 These studies show that megalin is expressed in hMSCs and is required for the bi

191 Binding to megalin is highly similar to gentamicin binding to calre

192 rush border of proximal kidney tubules where megalin is localized.

193 The interaction of GASP with megalin is mediated by the PDZ domain of GASP binding to

194 We tested the hypothesis that megalin is required for D actions in hMSCs with cells fr

195 Megalin is the major receptor in absorptive epithelial c

196 Megalin is the most abundant endocytic receptor in the p

197 rotein 330/megalin (hereafter referred to as megalin) is localized to the apical membrane domain of e

198 and proteins; ARH, a coat protein that binds megalin; LAMP2; and LC3.

199 diopathic Fanconi syndrome (n = 2) exhibited megalin levels within the normal range.

200 galin-mediated uptake of 125I-lactoferrin, a megalin ligand.

201 ion process, as has been described for other megalin ligands.

202 is a heparin-binding protein, as are several megalin ligands.

203 cycles to the basolateral membrane from CRE, Megalin, like pIgR, traffics to subapical Rab11-positive

204 inhibition pattern implied the presence of a megalin-like receptor.

205 C. elegans lrp-1 is a homolog of mammalian megalin, lipoprotein receptor-related protein (LRP) rece

206 pha,25(OH)(2)D(3) did so in hMSCs with lower megalin (lo-Meg, P < 0.001) or in si-Meg cells (P < 0.05

207 Megalin localizes to the apical surface of multiple epit

208 nsity lipoprotein receptor-related protein-2/megalin (LRP-2) is an endocytic receptor that is express

209 odelling to outline the recycling pathway of Megalin (LRP-2), an apical receptor with key development

210 Megalin (LRP-2/GP330), a member of the LDL receptor fami

211 mbers of the LDL receptor superfamily (LDLR, megalin, LRP).

212 id and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor.

213 Wnt4-CRE-driven megalin/LRP2 ablation in cystinotic mice efficiently blo

214 osis in which conditional excision of floxed megalin/LRP2 alleles in proximal tubular cells of cystin

215 These observations support a key role of the megalin/LRP2 pathway in the progression of nephropathic

216 whether receptor-mediated endocytosis by the megalin/LRP2 pathway of ultrafiltrated, disulfide-rich p

217 onfirmed that both mAb 10A3 and a known anti-megalin mAb immunoprecipitated and immunoblotted the sam

218 ate HDL endocytosis and further suggest that megalin may play a role in the intracellular trafficking

219 Moreover, megalin may play an important role in renal catabolism o

220 assembly of a multiprotein complex, in which megalin may serve a nonendocytic function in glomerular

221 ne-associated, carboxyl-terminal fragment of megalin (MCTF).

222 Megalin-mediated renal retention of radiolabeled somatos

223 Megalin-mediated transcytosis may regulate the extent of

224 s expressing megalin mini-receptors enhances megalin-mediated uptake of 125I-lactoferrin, a megalin l

225 Megalin mediates 25-hydroxyvitamin D(3) actions in human

226 um T3 levels, supporting the conclusion that megalin mediates Tg transcytosis.

227 uced by megalin competitors, indicating that megalin mediates Tg transcytosis.

228 In addition, knockdown of megalin mimicked all the effects of pathophysiologic alb

229 n Madin-Darby canine kidney cells expressing megalin mini-receptors enhances megalin-mediated uptake

230 Megalin mRNA was down-regulated in the KO embryonic spin

231 ands and interacting proteins in the cubilin-megalin multiligand endocytic receptor complex accounted

232 ay analysis included 12 genes in the cubilin-megalin multiligand endocytic receptor complex.

233 These observations provide evidence that a megalin N-terminal domain includes B and T cell epitopes

234 servations indicate that LRP-1 is related to megalin not only structurally but also functionally.

235 e absence of proximal tubule Sepp1 uptake in megalin null mice.

236 Evidence of Tg binding to megalin on FRTL-5 cells and on an immortalized rat renal

237 Physiologically, Tg binding to megalin on thyroid cells may be facilitated by Tg intera

238 somatostatin receptor-expressing CA20948 and megalin or cubilin receptor-expressing BN-16 cells, in t

239 ocytosis caused by a conditional deletion of megalin or the chloride channel ClC-5 had constitutively

240 We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significant

241 nd development in Caenorhabditis elegans and megalin plays a role in CNS development in zebrafish.

242 the gamma2 subunit of AP-1 had no effect on megalin polarity.

243 munohistochemical analysis demonstrated that megalin protein expression disappeared from the visceral

244 nsional structures of domains from the human megalin receptor been solved.

245 (p < .0001), implicating the involvement of megalin receptor in the internalization of the liposomes

246 LRP2, encoding the megalin receptor, was identified through connection with

247 odified with gentamicin (GM), a substrate to megalin receptors as we have shown in earlier studies, a

248 In a competition assay, inhibition of the megalin receptors resulted in a significant reduction in

249 esult indicates that Nrf2 may have a role in megalin regulation.

250 A genetic analysis of a gp330/megalin-related protein, LRP-1, has been undertaken in C

251 e postulate that the enzymatic processing of megalin represents part of a novel ligand-dependent sign

252 insect cell proteins produced a milder anti-megalin response and did not develop the disease.

253 erfere with the normal endocytic function of megalin, result in losses of potential ligands into the

254 oupling it to dynein; in the absence of ARH, megalin returns directly to the PM from EE via the conne

255 975232 (ApaI:A/C), rs731236 (TaqI:G/A)], and Megalin (rs3755166:G/A; rs2075252:C/T; rs4668123:C/T) ge

256 he role of clathrin and clathrin adaptors in megalin's apical localization and trafficking.

257 Consistent with megalin's being essential for development of mice, likel

258 by G protein-mediated signaling may regulate megalin's endocytic function and/or trafficking.

259 suggest that ANKRA may play a unique role in megalin's function as a clearance receptor in the kidney

260 eraction with GIPC/synectin was required for megalin's function, as megalin was mistargeted in the re

261 l four fragments stimulated proliferation of megalin-sensitized lymph node cells and induced high-tit

262 tibodies directed to the cytosolic domain of megalin showed a 35-40-kDa, membrane-associated, carboxy

263 togenesis, and for small interfering RNA for megalin (si-Meg) and control (si-Ctr).

264 Another finding was that Megalin SNP rs3755166:G/A was associated with greater de

265 ion between GIPC and the cytoplasmic tail of megalin suggest a model whereby G protein-mediated signa

266 R gene DAB2 and extends understanding of the megalin system in kidney function.

267 eping with the fact that the sequence of the megalin tail is unique.

268 juxtamembrane, 19-amino acid sequence on the megalin tail.

269 ken together, these results demonstrate that megalin-targeted liposomes may offer an opportunity to e

270 The objective of this study was to develop megalin-targeting liposome nanocarriers for placental dr

271 A mutant version of megalin that lacks the terminal valine is unable to bind

272 kD, variously named gp600, gp330, LRP-2, or "megalin." This study was performed to identify the regio

273 P < 0.01), and five of seven genes examined (megalin, thrombospondin-4, KR18, latrophilin-3, and phos

274 Targeting megalin thus offers an opportunity for the liposomes to

275 ibody almost completely inhibited binding of megalin to Tg, suggesting that the Tg region containing

276 s are consistent with defective recycling of megalin to the apical cell surface of the proximal tubul

277 ARH-mediated trafficking of megalin to the ERC is necessary for gamma-secretase medi

278 nuria, a condition consistent with defective megalin trafficking.

279 tion is associated with reduced abundance of megalin transport/signaling system and indicate that the

280 eriments were performed to determine whether megalin undergoes similar processing.

281 ey) and is also able to specifically bind to megalin via its fifth PDZ domain.

282 chanism that was inhibited by antagonists of megalin, viz. anti-receptor-associated protein and anti-

283 During embryonic development, megalin was found to be expressed along the apical surfa

284 ctin was required for megalin's function, as megalin was mistargeted in the renal proximal tubules of

285 e activity showed that N-Shh endocytosed via megalin was not efficiently targeted to the lysosomes fo

286 nding that the interaction between N-Shh and megalin was resistant to dissociation with low pH.

287 d that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003).

288 been reported to bind the endocytic receptor megalin, we explored the possibility that megalin acts i

289 taining a 563-residue N-terminal sequence of megalin were obtained from Escherichia coli and baculovi

290 ased the protein expression of renal tubular megalin, which inversely correlated with the urine album

291 igand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but w

292 However, megalin, which localizes primarily to the intermicrovill

293 at least in part, from reduced expression of megalin, which seems to occur without adverse effects an

294 Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes.

295 considered to represent specific binding to megalin, which was saturable and of high affinity (Kd ap

296 ovilli the majority of NHE3 was not bound to megalin, while in the dense vesicles most of the NHE3 co

297 no-terminal fragment of Shh (N-Shh) bound to megalin with high affinity.

298 Gentamicin binds to megalin with low affinity and exploits the common ligand

299 The association of megalin with MAGI-1 may allow the assembly of a multipro

300 , LDL-related protein 2 (LRP2, also known as megalin) with 25(OH)D3 and the C3 epimer of 25(OH)D3 [3-