CoChat
Sign Up
Cited by 53Wnt/β-catenin signaling in development and cancerCholesterol and Lipid MetabolismHeat shock proteins research

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index; 1 of the 28 sources its claims cite were checked for support.

Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding

Open access
Li, Yonghe, Chen, Jianglei, Lu, Wenyan, McCormick, Lynn M., Wang, Jianjun, Bu, Guojun·2005·Journal of Cell Science
DOI 10.1242/jcs.02651
Open this paper in CoChat — free accountOpen PDF

Abstract

Wnt co-receptors LRP5 and LRP6 are two members of the low-density lipoprotein receptor family. Receptor-associated protein is not only a specialized chaperone but also a universal antagonist for members of the low-density lipoprotein receptor family. Here we test whether Mesd, a newly identified chaperone for members of the low-density lipoprotein receptor family, also binds to mature receptors at the cell surface and antagonizes ligand binding. We found that Mesd binds to cell surface LRP5 and LRP6, but not to other members of the low-density lipoprotein receptor family. Scatchard analysis revealed that Mesd binds cell surface LRP6 with high affinity (Kd ∼3.3 nM). Interestingly, the C-terminal region of Mesd, which is absent in sequences from invertebrates, is necessary and sufficient for binding to mature LRP6, and is required for LRP6 folding. We also found that LRP6 is not a constitutively active endocytosis receptor and binding of the receptor-associated protein to LRP6 partially competes for Mesd binding. Finally, we demonstrated that Mesd antagonizes ligand binding to LRP6 at the cell surface. Together our results show that in addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Mesd binds mature LRP5/LRP6 at the cell surface with high affinity and can act as a receptor antagonist by blocking DKK1 binding to LRP6. Its C-terminal region is necessary and sufficient for LRP6 binding and is also required for LRP6 folding.

Key findings

  • Mesd binds cell surface LRP6 with a Kd of ~3.3 nM, and also binds LRP5, but not significantly to other LDLR-family members tested.
  • The C-terminal region of Mesd is necessary and sufficient for binding to mature LRP6; a Mesd mutant lacking this region fails to promote LRP6 maturation or enhance TCF/LEF transcriptional activity.
  • LRP6 is not a constitutively active endocytosis receptor; LRP6-expressing HT1080 cells showed 125I-Mesd degradation of 320 fmoles/mg cell protein after 4 hours at 37°C versus binding of 1320 fmoles/mg cell protein after 4 hours at 4°C.
  • Mesd completely blocked DKK1 binding to LRP6 at the cell surface, while RAP bound LRP6 with relatively low affinity and only partially competed for Mesd binding (~60% inhibition with 500 nM RAP versus >90% with 500 nM Mesd).

Methods

  • Cell surface binding assays used 125I-labeled Mesd, RAP, DKK1, and anti-HA IgG on LRP6-transduced HT1080 cells, control cells, HEK293 cells transfected with LDLR/LRP5/LRP6, LRP-null CHO cells expressing LRP minireceptors/VLDLR/apoER2, MEFs deficient in LRP and/or LDLR, and human cell lines MCF-7, U87, and aortic smooth muscle cells.
  • Binding affinity was assessed by saturation binding and Scatchard analysis; Mesd mutants were generated by PCR and tested for LRP6 binding, LRP6 folding by western blotting, and Wnt signaling by TOP-FLASH luciferase reporter assay.
  • LRP6 endocytosis was measured with 125I-anti-HA IgG internalization assays; DKK1 binding was examined by immunofluorescence and 125I-DKK1 binding/degradation assays.

Limitations

  • The paper states that Wnt3a binding to cell surface LRP6 and effects of exogenous Mesd on Wnt3a-induced signaling could not be consistently detected, and that the biological significance of the findings requires further investigation.
  • The paper notes that Mesd was not detected in concentrated conditioned media from several human cell lines, leaving open whether regulated Mesd secretion occurs only under certain physiological or pathophysiological conditions.
  • Evident from the text: most mechanistic conclusions rely on cultured cell lines and recombinant proteins, with no in vivo functional validation reported here.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1242/jcs.02651

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

1 of 28 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

Verify all 5 references — free account
  • Findingown data

    RAP binds to mature LRP6 at the cell surface.

    “RAP binds to mature LRP6 at the cell surface.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mesd binding to cell surface LRP6 does not significantly change the cytosolic β-catenin level.

    “Mesd binding to cell surface LRP6 does not significantly change the cytosolic ␤-catenin level, indicating that Mesd is unable to modify Wnt signaling by directly binding to LRP6 at the cell surface.”
    Quote in the paperSubstantial claim
  • Findingown data

    125I-Mesd reaches maximal binding after 2 hours at 4°C with LRP6-expressing HT1080 cells.

    “125 I-Mesd (5 nM) reached maximal binding after 2 hours incubation at 4°C with LRP6-expressing HT1080 cells (Fig. 1A).”
    Quote in the paperNot a substantial claim
  • Findingown data

    LRP6-mediated DKK1 degradation is inhibited by Mesd.

    “LRP6mediated DKK1 degradation is inhibited by Mesd.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mesd coexpression, but not MesdΔC coexpression, significantly enhanced TCF/LEF transcriptional activity in HEK293 cells.

    “As expected, Mesd coexpression, but not Mesd⌬C coexpression, significantly enhanced TCF/LEF transcriptional activity (Fig. 5B).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MesdΔC mutant is expressed and properly folded/trafficked, so its failure to support LRP6 maturation is due to loss of the C-terminal region rather than misfolding or lack of expression.
  • Probably not a substantial claim. 15
  • It may state two separate claims as one. 24
  • The quote only partly states this claim. 1

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8.

    “By using co-immunoprecipitation, several group reported that LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8 (Tamai et al., 2000;Mao et al., 2001;Kato et al., 2002;Itasaki et al., 2003;Liu et al., 2003).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Tamai et al., 2000 source
    • cites Mao et al., 2001

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Kato et al., 2002 source

      The Results section (“Lrp5 acts as a Wnt receptor in osteoblasts”; page unavailable) reports co-immunoprecipitation showing that Wnt1 and Wnt4 bind LRP5, not LRP6. Searches for LRP6 binding to Wnt1, Wnt3a, or Xenopus Wnt8 found no passage in our copy that establishes the claimed interactions. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one. The quote only partly states this claim.

    Findingown data

    The C-terminal region of Mesd is necessary and sufficient for binding to mature LRP6.

    “further truncation of the last 40 amino acids completely abolished LRP6 binding (Fig. 3B).”
    • Also stated in: § Mesd binds to mature LRP6 at the cell surface · plain
      “truncation of the N-terminal 11 amino acids of mouse Mesd had no effect on LRP6 binding”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Compared to control cells, LRP6-expressing HT1080 cells displayed ~20% increase of RAP binding, and this increase was abolished by excess unlabeled Mesd.

    “Compared to the control cells, LRP6 expressing HT1080 cells displayed ~20% increase of RAP binding, and this increase was abolished by excess unlabeled Mesd (Fig. 8A).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    RAP inhibits 125I-Mesd binding to LRP6 in a dose-dependent manner, with ~60% inhibition at 500 nM RAP, whereas 500 nM unlabeled Mesd inhibits >90%.

    “RAP inhibited 125 I-Mesd binding in a dose-dependent manner with ~60% inhibition achieved with 500 nM RAP, whereas the same concentration of unlabeled Mesd inhibited >90% of 125 I-Mesd binding (Fig. 8B).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    The increased DKK1 binding and degradation in LRP6-expressing cells were abolished by excess unlabeled Mesd, but not by excess unlabeled RAP.

    “The increased DKK1 binding and degradation were abolished by excess unlabeled Mesd, but not by excess unlabeled RAP (Fig. 9D,E).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    500 nM unlabeled Mesd completely, whereas 500 nM unlabeled RAP only partially, inhibited 125I-Mesd degradation.

    “When 125 I-Mesd (5 nM) uptake and degradation were performed, 500 nM unlabeled Mesd completely, whereas 500 nM unlabeled RAP only partially, inhibited 125 I-Mesd degradation (Fig. 8C).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    LRP6-transduced HT1080 cells exhibited 125I-Mesd degradation at 320 fmoles/mg after 4 hours at 37°C, whereas 125I-Mesd binding after 4 hours at 4°C was 1320 fmoles/mg.

    “HT1080 cells transduced with LRP6 exhibited 125 I-Mesd degradation at a level of 320 fmoles/mg cell protein after 4 hours of incubation at 37°C, whereas 125 I-Mesd binding following 4 hours of incubation at 4°C was detected at a level as high as 1320 fmoles/mg cell protein (Fig. 7).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Mesd binds to cell surface LRP5 and LRP6, but not to other members of the LDLR family.

    “We found that Mesd binds to cell surface LRP5 and LRP6, but not to other members of the low-density lipoprotein receptor family.”
    • Also stated in: § Mesd binds to mature LRP6 at the cell surface · plain
      “Interestingly, among the members of the LDLR family examined, only LRP5 specifically binds to Mesd, albeit at lower levels compared to LRP6 when these receptors were expressed at comparable levels (Fig. 2A).”
    • Also stated in: § Mesd binds to LRP5 and LRP6 at the cell surface · boosted
      “Thus, it is not surprising as demonstrated here that Mesd binds to cell surface LRP5 and LRP6, but not to other members of the LDLR family.”
    • Also stated in: § Mesd is a special chaperone for LRP5 and LRP6 · plain
      “Mesd binds to mature LRP5/6 but not significantly to other members of the LDLR family.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    The C-terminal region uniquely present in vertebrate Mesd is necessary and sufficient for binding to mature LRP6 at the cell surface.

    “In the present study, we found that this C-terminal region, uniquely present in vertebrate Mesd, is necessary and sufficient for binding to mature LRP6 at the cell surface.”
    • Also stated in: § Mesd is a special chaperone for LRP5 and LRP6 · plain
      “The C-terminal region of Mesd is necessary and sufficient for LRP6 binding.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationreasoning

    Mesd and RAP probably bind to different, but perhaps adjacent, sites on LRP6.

    “Thus, Mesd and RAP probably bind to different, but perhaps adjacent sites on LRP6.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Study design and conductreasoning

    To eliminate potential effects of LRP6 ligands on its internalization, 125I-anti-HA IgG was used for LRP6 endocytosis assays.

    “To eliminate potential effects of LRP6 ligands on its internalization, we utilized 125 I-anti-HA IgG for LRP6 endocytosis assays.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    The C-terminal region of Mesd is required for LRP6 folding and its signaling function at the cell surface.

    “Together, these results suggest that the C-terminal region of Mesd is required for LRP6 folding and its signaling function at the cell surface.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MesdΔC mutant is expressed and properly folded/trafficked, so its failure to support LRP6 maturation is due to loss of the C-terminal region rather than misfolding or lack of expression.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    RAP remains bound to LDLR family members to safeguard their trafficking through the early secretory pathway by antagonizing premature ligand binding.

    “However, RAP remains bound to the LDLR family members to safeguard their trafficking through the early secretory pathway by antagonizing premature ligand binding (Bu et al., 1995;Willnow et al., 1996).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bu et al., 1995

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Willnow et al., 1996 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    LRP5/6 has four β-propeller/EGF modules and three ligand-binding repeats.

    “LRP5/6 has four ␤-propeller/EGF modules and three ligand-binding repeats (Brown et al., 1998;Kim et al., 1998).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Brown et al., 1998 source
    • cites Kim et al., 1998 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    RAP exhibits high-affinity binding (KD ~1-10 nM) for LRP, megalin, the VLDLR and apoER2, but low affinity (KD ~250 nM) for the LDLR.

    “Studies have shown that RAP exhibits high-affinity binding (K D ~1-10 nM) for LRP, megalin, the VLDLR and apoER2, but low affinity (K D ~250 nM) for the LDLR (Bu, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bu, 2001

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    RAP binds with high affinity to LRP, megalin, VLDLR, and apoER2, and with lower affinity to LDLR, and inhibits binding of most known ligands of LDLR family members.

    “RAP, which binds with high affinity to LRP, megalin, very-low-density lipoprotein receptor (VLDLR), and apolipoprotein E receptor 2 (apoER2), and with a lower affinity to the LDLR, is able to inhibit the binding of most currently known ligands of LDLR family members (Bu, 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bu, 2001

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • It may state two separate claims as one.

    Premisecitation

    Mesd is a specialized chaperone for members of the LDLR family, required for folding of LRP5/LRP6.

    “More recently, two groups have identified a novel specialized chaperone for members of the LDLR family, termed Mesd (mesoderm development) in mouse (Hsieh et al., 2003) and Boca in Drosophila (Culi and Mann, 2003).”
    • Also stated in: § Introduction · plain
      “Mesd is specifically required for the maturation of these ␤-propeller/EGF modules through the secretory pathway (Culi et al., 2004).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hsieh et al., 2003 source
    • cites Culi and Mann, 2003 source
    • cites Culi et al., 2004 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    LRP5 and LRP6 lack the conserved NPXY motif but contain several putative di-leucine and YXX motifs.

    “Unlike other members of the LDLR family, LRP5 and LRP6 lack the conserved NPXY motif but contain several putative di-leucine and YXX (where is a bulky hydrophobic amino acid) motifs (Brown et al., 1998;Kim et al., 1998).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Brown et al., 1998 source
    • cites Kim et al., 1998 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    The LRP5 G171V mutation allows for autocrine Wnt signaling within intracellular compartments.

    “In this regard, it is interesting to note that the LRP5 mutation that causes high bone mass (G171V) disrupts LRP5 interaction with Mesd (Zhang et al., 2004) but allows for autocrine Wnt signaling within the intracellular compartments.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhang et al., 2004 source

  • It may state two separate claims as one.

    Interpretationown data

    Mesd binding to LRP6 at the cell surface does not trigger significant endocytosis, and little Mesd uptake and degradation can be detected.

    “These results suggest that Mesd binding to LRP6 at the cell surface does not trigger significant endocytosis, and consequently little Mesd uptake and degradation can be detected.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The 125I-anti-HA IgG binding to HA-tagged LRP6 does not itself induce LRP6 internalization, so the measured endocytosis reflects constitutive endocytosis.
    • Rests on an assumption: The observed 125I-Mesd degradation in LRP6-transduced HT1080 cells is mediated by LRP6 rather than by other receptors or nonspecific processes.

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    By binding to LRP6, DKK1 disrupts the binding of LRP6 to the Wnt/Frizzled ligand-receptor complex, and then inhibits Wnt/β-catenin signaling.

    “By binding to LRP6, DKK1 disrupts the binding of LRP6 to the Wnt/Frizzled ligand-receptor complex, and then inhibits Wnt/␤-catenin signaling (Semenov et al., 2001).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Semenov et al., 2001 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    A β-galactosidase-expressing vector was included as an internal control for transfection efficiency.

    “A ␤-galactosidaseexpressing vector (Promega, Madison, WI) was included as an internal control for transfection efficiency.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    MCF-7 cells express LRP at an undetectable level, whereas U87 cells and SMC express abundant LRP.

    “MCF-7 cells express LRP at an undetectable level, whereas U87 cells and SMC express abundant LRP (Li et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Li et al., 2003

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductown data

    The integrity of the subcloned DNA sequences was confirmed by DNA sequencing.

    “The integrity of the subcloned DNA sequence was confirmed by DNA sequencing.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    In addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6.

    “Together our results show that in addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Mesd and RAP probably bind to different, but perhaps adjacent sites on LRP6.

    “Together, these results suggest that Mesd and RAP probably bind to different, but perhaps adjacent sites on LRP6.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. It may state two separate claims as one.

    Premisecitation

    The TOP-FLASH luciferase reporter contains TCF-binding sites and can be directly activated by the β-catenin/TCF complex.

    “The TOP-FLASH luciferase reporter contains TCF-binding sites and can be directly activated by the ␤-catenin/TCF complex (Korinek et al., 1997).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Korinek et al., 1997 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Kremen proteins are DKK receptors that regulate Wnt/β-catenin signaling.

    “Kremen proteins are DKK receptors that regulate Wnt/␤-catenin signaling.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Mao et al., 2002 source
    • cites Davidson et al., 2002 source
    • cites Mao and Niehrs, 2003 source

  • It may state two separate claims as one.

    Premisecitation

    LRP6 is a cell surface receptor, and only the mature receptor can reach the cell surface and modulate Wnt signaling.

    “LRP6 is cell surface receptor, and only the mature receptor can reach the cell surface and modulate Wnt signaling (Cong et al., 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cong et al., 2004 source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Upon binding to DKK1, Kremen proteins are recruited into a complex with LRP6, which leads to rapid endocytosis and removal of LRP6 from the plasma membrane.

    “Upon binding to DKK1, Kremen proteins are recruited into a complex with LRP6, which leads to rapid endocytosis and removal of LRP6 from the plasma membrane.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Study design and conductcitation

    HA-tagged LRP minireceptor mLRP4 was used as a positive control and mLRP4tailess as a negative control for 125I-anti-HA IgG endocytosis.

    “We used HA-tagged LRP minireceptor mLRP4 as a positive control and mLRP4tailess (mLRP4 lacking the cytoplasmic tail) as a negative control for 125 I-anti-HA IgG endocytosis (Li et al., 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Li et al., 2000

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

31 of 31

  • The paper relies on this without support.

    MesdΔC mutant is expressed and properly folded/trafficked, so its failure to support LRP6 maturation is due to loss of the C-terminal region rather than misfolding or lack of expression.

    “we generated a Mesd mutant (Mesd⌬C), which lacks the Cterminal region (amino acids 156-191) but retains the ER retention signal (REDL) (Fig. 3A).”
    “In the presence of Mesd coexpression, but not of Mesd⌬C coexpression, the amount of the mature form of LRP6 was significantly increased (Fig. 5A).”

  • The paper relies on this without support.

    The 125I-anti-HA IgG binding to HA-tagged LRP6 does not itself induce LRP6 internalization, so the measured endocytosis reflects constitutive endocytosis.

    “To eliminate potential effects of LRP6 ligands on its internalization, we utilized 125 I-anti-HA IgG for LRP6 endocytosis assays.”
    “Interestingly, we found that the endocytosis rate of LRP6 was extremely slow, and was indistinguishable from that of mLRP4tailess (Fig. 6B), indicating that LRP6 itself is unable to initiate endocytosis.”

  • The paper relies on this without support.

    The observed 125I-Mesd degradation in LRP6-transduced HT1080 cells is mediated by LRP6 rather than by other receptors or nonspecific processes.

    “HT1080 cells transduced with LRP6 exhibited 125 I-Mesd degradation at a level of 320 fmoles/mg cell protein after 4 hours of incubation at 37°C, whereas 125 I-Mesd binding following 4 hours of incubation at 4°C was detected at a level as high as 1320 fmoles/mg cell protein (Fig. 7).”

  • The paper relies on this without support.

    Direct modulation of LRP6-mediated Wnt signaling would change cytosolic β-catenin levels.

    “Mesd binding to cell surface LRP6 does not significantly change the cytosolic ␤-catenin level, indicating that Mesd is unable to modify Wnt signaling by directly binding to LRP6 at the cell surface.”

  • The paper relies on this without support.

    In vitro binding of Mesd to cell surface LRP6 and competition with DKK1 reflect a physiological role in regulating LRP5/6 function.

    “However, the ability of Mesd in modulation DKK1 binding to LRP6 suggests that Mesd may have a physiological role in the regulation of LRP5/6 function at the cell surface.”

  • The paper relies on this without support.

    Cell surface binding of Mesd to LRP6 and its antagonism of DKK1 binding indicate that Mesd may safeguard mature LRP5/6 in the secretory and/or endocytic pathways.

    “Results from our current studies suggest that Mesd may also possess this feature.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Mesd(150-195) is described as the last 45 amino acids

    Minor

    Residues 150 through 195 inclusive comprise 46 amino acids, not 45. The stated length of the binding fragment therefore disagrees with its residue range in Figure 4.

  • Figure 9E names the wrong radiolabeled protein

    Minor

    The results and Figure 9E heading describe DKK1 degradation, but the figure caption says the degradation assay used radiolabeled Mesd. That leaves the identity of the measured protein inconsistent for a result supporting the conclusion that Mesd inhibits DKK1 degradation.

  • Figure 5A and results name different blotting antibodies

    Minor

    The results say the LRP6 forms in Figure 5A were detected with anti-MYC, whereas the figure caption says the blots used anti-FLAG or anti-HA.

3 of 3

Citations

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Metadata

Authors
Li, Y., Chen, J., Lu, W., McCormick, L. M., Wang, J., & Bu, G.
Affiliations
  • St. Louis Children's Hospital (US)
  • Southern Illinois University Carbondale (US)
  • Department of Pediatrics, St Louis Children's Hospital, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Corresponding author
Li, Yonghe
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2005-11-15
Volume
118
Issue
22
Pages
5305-5314
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.02651
OpenAlex
W2140997828
Semantic Scholar
9ff3b1b6494bd867d372e6f288201f9016f2e4ab
Cited by
53
References
52
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
1.55
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061761)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
LRP6, LRP5, low-density lipoprotein receptor family, receptor-associated protein, molecular chaperones, receptor antagonists, ligand binding inhibition, receptor folding, C-terminal domain, Wnt signaling
MeSH terms
Animals, Binding, Competitive, Cell Membrane, Cytosol, Endocytosis, Fibroblasts, Humans, Ligands, Protein Binding, Protein Processing, Post-Translational, Molecular Chaperones, LDL-Receptor Related Proteins, LDL-Receptor Related Protein-Associated Protein, Myocytes, Smooth Muscle, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, beta Catenin, Mice, Low Density Lipoprotein Receptor-Related Protein-6

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review