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Cited by 292Genetics and Neurodevelopmental DisordersAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein

Open access
Westmark, Cara J, Malter, James S·2007·PLoS Biology
DOI 10.1371/journal.pbio.0050052PMC PMC1808499
Open this paper in CoChat — free accountOpen PDF

Abstract

Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Abeta) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome. Here we show that FMRP binds to the coding region of APP mRNA at a guanine-rich, G-quartet-like sequence. Stimulation of cortical synaptoneurosomes or primary neuronal cells with the metabotropic glutamate receptor agonist DHPG increased APP translation in wild-type but not fmr-1 knockout samples. APP mRNA coimmunoprecipitated with FMRP in resting synaptoneurosomes, but the interaction was lost shortly after DHPG treatment. Soluble Abeta40 or Abeta42 levels were significantly higher in multiple strains of fmr-1 knockout mice compared to wild-type controls. Our data indicate that postsynaptic FMRP binds to and regulates the translation of APP mRNA through metabotropic glutamate receptor activation and suggests a possible link between Alzheimer disease and fragile X syndrome.

AI snapshot

Written from the paper’s full text.

TL;DR

This study reports that FMRP binds APP mRNA in its coding region and represses its synaptic translation; mGluR5 activation by DHPG releases FMRP and rapidly increases APP synthesis in wild-type but not fmr-1 knockout preparations. fmr-1 knockout mice show constitutively elevated APP and increased brain Aβ40/Aβ42, suggesting a mechanistic link between fragile X syndrome and Alzheimer disease–related amyloid pathology.

Key findings

  • FMRP coimmunoprecipitated with APP mRNA in resting wild-type synaptoneurosomes, but the interaction was lost after DHPG treatment (>60-fold difference by RT-qPCR); DHPG increased APP translation 2.7-fold at 15 min and 1.6-fold at 60 min in WT synaptoneurosomes, with no comparable response in fmr-1 KO samples. Anisomycin and the mGluR5 inhibitor MPEP blocked DHPG-mediated APP synthesis.
  • Steady-state APP was constitutively higher in KO synaptoneurosomes; DHPG raised WT APP levels 1.6–1.8-fold within 5–20 min. In cultured cortical neurons, basal dendritic APP was 21% higher in fmr-1 KO than WT, and DHPG increased WT dendritic APP by 18%–25% but did not increase it in KO neurons.
  • Binding mapped to a G-rich coding-region sequence at nucleotides 699–796, which was approximately 4-fold more protected from RNase T1 digestion and approximately 5-fold greater by modified CLIP than the predicted downstream G-quartet motif (825–846). APP mRNA did not decay over 120 min regardless of mGluR activation.
  • Aβ40/Aβ42 were elevated in fmr-1 KO brains: FVB mice showed 1.6 times more soluble Aβ40 and 2.5 times more soluble Aβ42 than WT; C57BL/6 mice showed 2.8-fold more guanidine-soluble Aβ40 and 1.2-fold more guanidine-soluble Aβ42, while soluble Aβ40/42 were not increased in that strain.

Methods

  • WT and fmr-1 KO mouse cortical synaptoneurosomes from 14–17-day-old pups and embryonic day 18 primary cortical neurons were stimulated with 100 μM DHPG; most experiments used FVB mice, while cultured neurons and some Aβ ELISAs used C57BL/6 mice.
  • New APP synthesis was measured by 35S-Met labeling and anti-APP immunoprecipitation; steady-state APP by Western blot; dendritic APP by immunofluorescence/confocal microscopy; FMRP–APP mRNA interaction by FMRP immunoprecipitation with RT-qPCR, RNase T1 protection, and modified CLIP; Aβ40/42 by ELISA.
  • Analyses used t-tests with reported p-values; sample sizes were generally n = 3–6 for translation and interaction experiments, and Aβ ELISAs used n = 4 WT/3 KO FVB and n = 4 WT/4 KO C57BL/6 mice aged 11–14 months.

Limitations

  • Stated: only a limited number of aged human FXS brains have been studied, so increased amyloid burden and synaptic degeneration in human FXS cannot be excluded; cognitive decline is difficult to measure in mentally retarded individuals. Some supporting data are described as unpublished.
  • Evident: Aβ increases were strain- and fraction-dependent—C57BL/6 soluble Aβ40/42 were not increased, and some Aβ comparisons were not statistically significant (FVB Aβ40 p = 0.06; C57BL/6 guanidine-soluble Aβ42 p = 0.39)—with small sample sizes. The proposed link between FXS and AD is correlative, not causal.

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

Integrity signals

Registry

Crossref · 10.1371/journal.pbio.0050052

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

11 of 26 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    DHPG does not increase overall protein synthesis in synaptoneurosomes.

    “However, we did not observe an increase in overall protein synthesis in response to DHPG, whereas Weiler and colleagues [31] observed a 1.3-fold increase in 35S-Met incorporation after 5 min of stimulation.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [31] Weiler, 2004, Proc Natl Acad Sci U S A source

      The citation is attached to the statement that Weiler and colleagues observed a 1.3-fold increase in 35S-Met incorporation after five minutes; the preceding statement that no increase was observed is the citing authors’ own result. The available indexed passages have no results section or page text reporting DHPG stimulation or incorporation, and searches for those terms and the 1.3-fold figure found no relevant passage. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • Findingcitation

    APP mRNA lacks a kissing complex site for FMRP.

    “FMRP also binds to kissing complex sites [18], but APP mRNA lacks such a site.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [18] Darnell, 2005, Genes Dev source
  • Interpretationown data

    FMRP is not required for basal protein synthesis.

    “Therefore, FMRP was not required for basal protein synthesis, which is in agreement with a prior report [31].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [31] Weiler, 2004, Proc Natl Acad Sci U S A source

      The passages available from our copy are bibliographic material, including the title, which concerns neurotransmitter-activated translation at synapses. Searches for basal, unstimulated, and baseline protein synthesis found no passage addressing whether FMRP is required for basal synthesis. (LLM, conf=0.70)

      Experimental — accuracy not yet measured
  • Interpretationcitation

    mGluR activation rapidly derepresses APP synthesis.

    “mGluR activation rapidly derepresses APP synthesis as shown for FMRP and PSD-95 [21,22].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [21] Greenough, 2001, Proc Natl Acad Sci U S A source

      The Abstract reports that mGluR agonist stimulation increased FMRP in synaptoneurosomes within 2–5 minutes, supporting the FMRP example attached to this citation. It does not report APP synthesis or establish that the increase occurs through derepression. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [22] Todd, 2003, Proc Natl Acad Sci U S A source
  • Findingown data

    In human APP mRNAs, the G-rich region containing the putative G-quartet motif is found in all three splice variants APP695, APP751, and APP770.

    “In the human APP mRNAs, the G-rich region containing the putative G-quartet motif is found in all three splice variants (APP695, APP751, and APP770; 87 nucleotides upstream of the sequence coding for the Kunitz-type protease inhibitor domain, which is missing in APP695).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 19
  • May combine two claims. 17
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    DHPG stimulates dendritic translation of FMRP.

    “In fact, in both assays there was more FMRP immunoprecipitated from the DHPG-treated WT SNs, which is in agreement with previous reports that DHPG stimulates the dendritic translation of FMRP [22,39].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [22] Todd, 2003, Proc Natl Acad Sci U S A source

      The Results (page not available) show that DHPG increased FMRP in cortical neurons and that a protein-synthesis inhibitor blocked the increase. The same section reports DHPG-induced FMRP translation in synaptoneurosomes, but the paper does not establish that the new FMRP was translated specifically within dendrites. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [39] Weiler, 1997, Proc Natl Acad Sci U S A source

  • Classified as probably not a substantial claim.

    Premisecitation

    FMRP is required for type 1 mGluR-dependent translation of synaptic proteins, including FMRP and PSD-95.

    “FMRP is required for type 1 metabotropic glutamate receptor (mGluR)–dependent translation of synaptic proteins, including FMRP and postsynaptic density 95 (PSD-95) [21,22].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [21] Greenough, 2001, Proc Natl Acad Sci U S A source

      The paper’s Abstract reports that group I mGluR stimulation induces synaptoneurosomal protein synthesis, including FMRP, and that this response is dramatically reduced in mice lacking full-length FMRP. It describes FMRP as possibly involved in or required for the response, rather than establishing an unqualified requirement. No passage found for PSD-95 or postsynaptic density 95 supports its inclusion. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [22] Todd, 2003, Proc Natl Acad Sci U S A source

      The Discussion reports that type-I mGluR activation rapidly induces translation of both FMRP and PSD-95, while the knockout result supports a requirement for FMRP in PSD-95 translation. The Results also show mGluR-dependent production of FMRP, but the paper does not establish that FMRP is required for its own mGluR-dependent translation. Page numbers are not available in the supplied passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Overexpression of APP and its proteolytic product Aβ have been implicated in the synaptic losses seen early in the development of AD.

    “Conversely, overexpression of APP and its proteolytic product, Aβ, have been implicated in the synaptic losses seen early in the development of AD [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Lacor, 2004, J Neurosci source

      The Introduction (page unavailable) links soluble Aβ oligomers to early synapse failure and notes their elevation in hAPP transgenic mice. The Discussion (page unavailable) proposes that oligomers may cause physical synaptic degeneration and reports terminal loss in some transgenic models, but it does not establish that APP overexpression itself causes the synaptic losses claimed, or that physical synapse loss occurs early in human AD. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Nucleolin interacts with FMRP to form multiprotein complexes.

    “Since nucleolin interacts with FMRP to form multiprotein complexes [38], we would expect the 29-base element to be protected from T1 ribonuclease digestion of anti-FMRP IPs, as shown in Figure 7A (nt 2318–2416).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] Ceman, 1999, Mol Cell Biol source

  • May combine two claims.

    Findingown data

    DHPG stimulation increases APP translation in WT cortical synaptoneurosomes but not in fmr-1 KO samples.

    “Stimulation of cortical synaptoneurosomes or primary neuronal cells with the metabotropic glutamate receptor agonist DHPG increased APP translation in wild-type but not fmr-1 knockout samples.”
    • Also stated in: § FMRP Regulates APP Translation · plain
      “After 15 min of incubation, untreated WT SNs translated modest amounts of APP, which rapidly increased by 2.7-fold with DHPG treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DHPG stimulation increases dendritic APP levels in WT primary cortical neurons but not in fmr-1 KO neurons.

    “Neurons stimulated with DHPG for 10 and 20 min prior to cell fixation showed a 18%–25% increase in dendritic APP levels in WT but no increase in fmr-1 KO cultures (Figure 5B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In middle-aged FVB fmr-1 KO mice, soluble Aβ40 is 1.6-fold and Aβ42 is 2.5-fold higher than in WT controls.

    “The fmr-1 KO mouse brain contained 1.6 times more Aβ40 and 2.5 times more Aβ42 than WT controls (Figure 8A).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The average PCR efficiencies for the APP and 18S primers over a 200-fold concentration range were 100% (APP) and 101% (18S) (n = 9 experiments each), with a delta slope of 0.079.

    “The average PCR efficiencies for the APP and 18S primers over a 200-fold concentration range were 100% (APP) and 101% (18S) (n = 9 experiments each), with a delta slope of 0.079.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In C57BL/6 fmr-1 KO mice, soluble Aβ40 or Aβ42 levels are not increased, but guanidine-soluble fractions show a 2.8-fold increase in Aβ40 and a 1.2-fold increase in Aβ42.

    “We did not observe an increase in soluble Aβ40 or Aβ42 levels in fmr-1 KO C57BL/6 brain samples (unpublished data), but guanidine-soluble fractions showed a 2.8-fold increase in Aβ40 and a 1.2-fold increase in Aβ42 (Figure 8B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    APP mRNA is present in synaptoneurosomes and coimmunoprecipitates with anti-FMRP but not control antisera in cortical lysates and synaptoneurosomes.

    “Contrary to a previous report utilizing a different protocol for the preparation of SNs [26], APP mRNA is present in SNs, and reverse transcription (RT)–PCR revealed that the message was brought down with specific, but not control, antisera in cortical lysates as well as SNs (unpublished data).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Sung, 2004, Brain Res Mol Brain Res source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Western blotting of a duplicate membrane indicated that FMRP migrates at 80 kDa.

    “Western blotting of a duplicate membrane indicated that FMRP migrates at 80 kDa.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The third band from the top of the percoll gradient (the 23%/15% interface) contained intact synaptoneurosomes.

    “The third band from the top of the gradient (the 23%/15% interface) containing intact SNs was removed and pooled for the experiments.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    FMRP binds to G-rich sequences (G-quartets) with consensus site DWGG-N(0-2)-DWGG-N(0-1)-DWGG-N(0-1)-DWGG.

    “FMRP binds to G-rich sequences (so-called G-quartets; consensus site: DWGG-N(0–2)-DWGG-N(0–1)-DWGG-N(0–1)-DWGG, where D is any nucleotide except C and W is A or U) [17] arranged in a planar conformation and stabilized by Hoogsteen-type hydrogen bonds.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Darnell, 2001, Cell source

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    The two higher-molecular-weight bands at the 15%/10% and 10%/3% interfaces contained broken membranes.

    “The two higher-molecular-weight bands at the 15%/10% and 10%/3% interfaces contain broken membranes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    FMRP acts as an immediate early-response protein that regulates translation at the synapse.

    “Our data support a model developing in the literature whereby FMRP acts as an immediate early-response protein that regulates translation at the synapse.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    APP localizes to postsynaptic densities, axons, dendrites, and neuromuscular junctions.

    “APP localizes to postsynaptic densities, axons, dendrites, and neuromuscular junctions [1,46].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Akaaboune, 2000, Mol Cell Neurosci source
    • cites [46] Shigematsu, 1992, Brain Res source

  • May combine two claims.

    Study design and conductown data

    Synaptoneurosomes from WT and fmr-1 KO mice are metabolically active with equivalent total 35S-Met incorporation.

    “SNs from either animal were metabolically active with equivalent total 35S-Met incorporation (Figure 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    BLAST homology searches of the amplicons revealed that the primers were gene specific.

    “BLAST homology searches of the amplicons revealed that the primers were gene specific.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Nucleolin and hnRNP C bind to the 29-base element in APP mRNA.

    “We have also identified two proteins, nucleolin and hnRNP C, that bind to this 29-base element [40].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Zaidi, 1995, J Biol Chem

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

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The final APP and 18S PCR products were single bands of the correct molecular weight (74 bp for APP; 84 bp for 18S) by EtBr staining.

    “The final APP and 18S PCR products were analyzed by agarose gel electrophoresis and were single bands of the correct molecular weight by EtBr staining (74 bp for APP; 84 bp for 18S).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Brains of two distinct murine strains lacking fmr-1 both show increased APP and accumulated pathogenic Aβ species over time.

    “Therefore, the brains of two distinct murine strains lacking fmr-1 both showed increased APP and accumulated pathogenic Aβ species over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    FMRP represses translation of APP mRNA in dendrites, suggesting a link between FXS and autism and AD.

    “In conclusion, FMRP represses translation of APP mRNA in dendrites, suggesting a link between two neurodevelopmental disorders, FXS and autism, and a neurodegenerative disease, AD.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Interpretationown data

    FMRP represses translation of APP mRNA in dendrites through mGluR-dependent interactions with APP mRNA.

    “Our data indicate that FMRP represses the translation of APP through mGluR-dependent interactions with APP mRNA.”
    • Also stated in: § Discussion · hedged
      “In conclusion, FMRP represses translation of APP mRNA in dendrites, suggesting a link between two neurodevelopmental disorders, FXS and autism, and a neurodegenerative disease, AD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Because the difference in slopes between the APP and 18S PCRs was less than 0.1, the comparative CT method was used to calculate relative APP mRNA normalized to 18S rRNA.

    “As the difference in slopes between the sample PCR (APP) and the normalization control (18S) was less than 0.1, the comparative CT method was utilized to calculate the relative concentration of APP mRNA normalized to 18S rRNA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Loss of FMRP/APP mRNA interaction results in rapid, pulsatile protein expression in dendrites.

    “Presumably, the loss of FMRP/APP mRNA interaction results in rapid, pulsatile protein expression in dendrites.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Excess Aβ causes impaired synaptic function.

    “APP is likely important for synapse formation in the developing brain [1], while excess Aβ causes impaired synaptic function [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Kamenetz, 2003, Neuron source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    APP is likely important for synapse formation in the developing brain.

    “APP is likely important for synapse formation in the developing brain [1], while excess Aβ causes impaired synaptic function [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Akaaboune, 2000, Mol Cell Neurosci source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    fmr-1 KO mice display dendritic spine anomalies similar to those in human FXS.

    “We utilized fmr-1 KO mice, a rodent model for FXS, that display dendritic spine anomalies similar to that in the human disorder [28–30].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [28]

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

    • cites [29] Irwin, 2001, Am J Med Genet source
    • cites [30] McKinney, 2005, Am J Med Genet B Neuropsychiatr Genet source

  • May combine two claims.

    Premisecitation

    APP/APP-like protein 2 double-KO mice exhibit defective neuromuscular junctions, excessive nerve terminal sprouting, and defective synaptic transmission.

    “APP/APP-like protein 2 double-KO mice exhibit defective neuromuscular junctions, excessive nerve terminal sprouting, and defective synaptic transmission [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Wang, 2005, J Neurosci source

  • May combine two claims.

    Interpretationown data

    Physical interactions between FMRP and APP mRNA underlie translational repression, with mGluR activation rapidly moderating these events.

    “Our data suggest that physical interactions between FMRP and APP mRNA underlie translational repression, with mGluR activation rapidly moderating these events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    APP mRNA is a potential target of FMRP, presumably via the coding region putative G-quartet.

    “Thus, APP mRNA is a potential target of FMRP, presumably via the coding region putative G-quartet.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    fmr-1 genotypes were determined by PCR analysis of DNA extracted from tail biopsies.

    “fmr-1 genotypes were determined by PCR analysis of DNA extracted from tail biopsies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Upon mGluR activation, FMRP is released from the nontranslating RNP, resulting in prompt protein synthesis.

    “Upon mGluR activation, FMRP is released from the nontranslating RNP, resulting in prompt protein synthesis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The fmr-1 KO mice used were backcrossed more than 11 times to FVB mice, and these FVB mice carry genes for pigmentation and normal vision.

    “The fmr-1 KO mice were originally developed by Frank Kooy and backcrossed >11 times to FVB mice, albeit these FVB mice have the genes for pigmentation and normal vision [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28]

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

34 of 34

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.

  • Abstract claims increased soluble Aβ in multiple strains

    Major

    The abstract says soluble Aβ40 or Aβ42 was significantly higher in multiple knockout strains, but the Results report no increase in either soluble species in the C57BL/6 strain. The increase reported for that strain was in a separate guanidine-soluble fraction.

  • CLIP assay sample differs between Results and Methods

    Major

    The Results say synaptoneurosomes were cross-linked for the modified CLIP assay, while the Methods say the cross-linked material was cleared cortical lysate.

2 of 2

Cites

Flagged first, then by citations

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Authors
Westmark, C. J., & Malter, J. S.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Westmark, Cara J
ORCID
Venue
PLoS Biology
Publisher
Public Library of Science (PLoS)
Published
2007-02-13
Volume
5
Issue
3
Pages
e52
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.0050052
PMC
PMC1808499
OpenAlex
W2055557113
Cited by
292
References
60
Citations by year
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FWCI
7.86
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
FMRP, amyloid precursor protein, mGluR5, mRNA-binding proteins, G-quartet, amyloid-beta, Alzheimer's disease, fragile X syndrome
MeSH terms
Animals, Base Sequence, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Inbred C57BL, Molecular Sequence Data, RNA, Messenger, Sequence Homology, Nucleic Acid, Protein Biosynthesis

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-27.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-27.

Cited sources are checked by 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 ›

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