ライフサイエンスコーパス: megalin

1 d hormones is encountered in animals lacking megalin.

2 ibodies from rats with AHN induced by native megalin.

3 ional or other structural features of native megalin.

4 pitation assays, GST-GIPC specifically binds megalin.

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

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

7 proximal tubule epithelia which also express megalin.

8 esicles most of the NHE3 coprecipitated with megalin.

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

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

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

12 d and immunoblotted the same protein, namely megalin.

13 that Tg endocytosis is partially mediated by megalin.

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

15 own to inhibit the binding of all ligands to megalin.

16 cidin staining in proximal tubules that lack megalin.

17 e renal proximal tubule by another receptor, megalin.

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

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

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

21 membrane proteolysis (RIP) and expression of megalin.

22 toxicity, entering the cell via the receptor 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 Megalin also binds the receptor-associated protein (RAP)

42 In ligand blotting assays, megalin also bound several other low molecular weight po

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

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 Megalin and cubilin levels detected by immunochemilumine

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

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

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

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

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

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

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

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

57 nsional model describing the complex between megalin and gentamicin.

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

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

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

61 ce the Heymann nephritis autoantigen, gp330 (megalin), and an associated protein of 45 kd (RAP).

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

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

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

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

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

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

68 Furthermore, megalin antisense oligodeoxynucleotide treatment resulte

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

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

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

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

73 in vertebrate VgRs, insect VgR/YPRs, and LRP/megalins are not directly homologous with one another.

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 ne-S-transferase fusion protein (RAP-GST) to megalin at the surface of L2 yolk sac carcinoma cells an

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

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

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

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

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

85 taining the peptide sequence is required for megalin binding.

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

87 cients, a 9.6 S megalin-free form and a 21 S megalin-bound form, and that when NHE3 assembles with me

88 Megalin-bound Tg was releasable by heparin.

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

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

91 y with its respective antigen and with whole megalin by immunoblotting.

92 e a characteristic brush-border staining for megalin by indirect immunofluorescence on rat kidney.

93 We identified a ligand-binding site on megalin by raising mAb against purified megalin, selecte

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

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

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

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

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

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

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

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

102 the amount released was markedly reduced by megalin competitors.

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

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

105 ibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-C

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

107 The cytoplasmic tail of megalin contains two FXNPXY motifs.

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

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

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

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

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

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

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

115 (99m)Tc-DMSA is thus critically dependent on megalin/cubilin receptor function and therefore is a mar

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

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

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

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

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

121 99m)Tc-DMSA was identified in scintigrams of megalin/cubilin-deficient mice.

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

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

124 Hence, Megalin defines the apical recycling pathway of epitheli

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

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

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

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

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

130 Similarly, the LRP/megalins did not arise from the duplication of a two-clu

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

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

133 Megalin enters polarized MDCK cells through segregated a

134 ound form, and that when NHE3 assembles with megalin, epitopes within the carboxyl-terminal 131 amino

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

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

137 Cubilin and megalin exhibited coincident patterns of mRNA expression

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

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

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

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

142 Megalin expression at the luminal membrane is reduced by

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

144 Megalin expression remained unaltered in adult WT and KO

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

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

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

148 was associated with preservation of cortical megalin expression.

149 odies raised against each of the recombinant megalin fragments reacted preferentially with its respec

150 distinct sedimentation coefficients, a 9.6 S megalin-free form and a 21 S megalin-bound form, and tha

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

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

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

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

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

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

157 Megalin (gp330) is the main target antigen involved in t

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

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

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

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

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

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

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

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

166 rotein lipase, aprotinin, and lactoferrin to megalin in a concentration-dependent manner.

167 first demonstrated that FRTL-5 cells express megalin in a thyroid-stimulating hormone-dependent manne

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

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

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

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

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

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

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

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

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

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

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

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

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

181 Immunization with megalin induces active Heymann nephritis, which reproduc

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

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

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

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

186 Megalin is a complex immunological target with four disc

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

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

189 To begin to address how megalin is able to bind ligands with unique structurally

190 ochemical procedures, it was also shown that megalin is able to internalize insulin into endocytic ve

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

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

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

194 Megalin is an endocytic receptor that binds multiple lig

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

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

197 megalin, selected for a mAb whose binding to megalin is inhibited by RAP, and mapped the epitope for

198 the second ligand-binding domain (LBD II) of megalin is involved in the pathogenesis of passive HN be

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

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

201 delivered to lysosomes and degraded whereas megalin is recycled to the cell surface.

202 Megalin is the major receptor in absorptive epithelial c

203 Megalin is the most abundant endocytic receptor in the p

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

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

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

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

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

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

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

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

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

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

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

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

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

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

218 sites recognized by the LDL receptor and by megalin may be different.

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

220 These data suggest that megalin may play a significant role as a renal reabsorpt

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

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

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

224 Megalin-mediated renal retention of radiolabeled somatos

225 Megalin-mediated transcytosis may regulate the extent of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

244 To investigate the fate of megalin/RAP complexes, we bound RAP glutathione-S-transf

245 We show that megalin/RAP-GST complexes, which are internalized via cl

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

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

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

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

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

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

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

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

254 975232 (ApaI:A/C), rs731236 (TaqI:G/A)], and Megalin (rs3755166:G/A; rs2075252:C/T; rs4668123:C/T) ge

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

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

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

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

259 e on megalin by raising mAb against purified megalin, selected for a mAb whose binding to megalin is

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

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

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

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

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

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

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

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

268 t was demonstrated that this binding site is megalin, the large multiligand binding endocytic recepto

269 the ligand, lipoprotein lipase, was bound to megalin, the receptor was found to recycle through early

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

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

272 The ability of megalin to mediate cellular endocytosis of Lp B-70.5 was

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

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

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

276 nuria, a condition consistent with defective megalin trafficking.

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

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

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

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

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

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

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

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

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

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

287 four cysteine-rich ligand-binding repeats in megalin were expressed in a baculovirus system and immun

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

289 luster, and LDLR-related proteins (LRPs) and megalins which have four clusters of 2-7, 8, 10, and 11

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-