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Cited by 17Cellular transport and secretionNeuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental Disorders

The DOI matches its Crossref record; 96 of the 96 references it cites were found in a registry or an index; 32 of the 62 sources its claims cite were checked for support.

Recruitment of the SNX17-Retriever recycling pathway regulates synaptic function and plasticity

Open access
Rivero-Ríos, Pilar, Tsukahara, Takao, Uygun, Tunahan, Chen, Alex, Chavis, Garrett D., Giridharan, Sai Srinivas Panapakkam, Iwase, Shigeki, Sutton, Michael A., Weisman, Lois S.·2023·Journal of Cell Biology
DOI 10.1083/jcb.202207025PMC PMC10165670

Published version of a preprint

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Abstract

Trafficking of cell-surface proteins from endosomes to the plasma membrane is a key mechanism to regulate synaptic function. In non-neuronal cells, proteins recycle to the plasma membrane either via the SNX27-Retromer-WASH pathway or via the recently discovered SNX17-Retriever-CCC-WASH pathway. While SNX27 is responsible for the recycling of key neuronal receptors, the roles of SNX17 in neurons are less understood. Here, using cultured hippocampal neurons, we demonstrate that the SNX17 pathway regulates synaptic function and plasticity. Disruption of this pathway results in a loss of excitatory synapses and prevents structural plasticity during chemical long-term potentiation (cLTP). cLTP drives SNX17 recruitment to synapses, where its roles are in part mediated by regulating the surface expression of β1-integrin. SNX17 recruitment relies on NMDAR activation, CaMKII signaling, and requires binding to the Retriever and PI(3)P. Together, these findings provide molecular insights into the regulation of SNX17 at synapses and define key roles for SNX17 in synaptic maintenance and in regulating enduring forms of synaptic plasticity.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Rivero-Ríos et al. show that the SNX17-Retriever endosomal recycling pathway localizes to excitatory synapses and is recruited there during chemical LTP via NMDAR-CaMKII signaling and PI(3)P. This recruitment is required for dendritic spine maintenance and cLTP-induced structural/functional plasticity, partly through SNX17-dependent surface recycling of β1-integrin.

Key findings

  • SNX17, VPS35L, and COMMD1 colocalize with excitatory synapses; SNX17 was present in 44.6 ± 6.0% of PSD95/vGLUT1-defined synapses. SNX17 knockdown reduced mEPSC frequency by ∼51.2% (clone 1) and 50.6% (clone 2) without changing amplitude, and reduced spine density by 37.5% (0.483 to 0.302 spines/μm); VPS26C knockdown similarly reduced spine density.
  • cLTP drove transient synaptic recruitment of SNX17 and VPS35L: SNX17 colocalization rose from 43.31 ± 1.881% at baseline to 51.75 ± 1.520% at 10 min and 49.93 ± 1.533% at 30 min, returning to 39.68 ± 1.625% at 60 min. Recruitment required NMDAR Ca²⁺ and CaMKII (blocked by BAPTA-AM, D-APV, and AIP; not by nifedipine, KT5720, or U0126), and CaMKII-T286D was sufficient to drive SNX17 to spines.
  • SNX17 knockdown blocked cLTP-induced increases in mEPSC amplitude/frequency and spine head enlargement; the Retriever-binding-deficient SNX17-L470G mutant failed to recruit to spines and failed to rescue cLTP spine enlargement.
  • SNX17 knockdown reduced surface β1-integrin by 42.4 ± 3.1%; cLTP increased surface β1-integrin in control but not SNX17 knockdown neurons. ITGB1 knockdown reduced spine density by 28.2%, and β1-integrin blocking prevented cLTP-induced spine enlargement and maintenance of mEPSC changes from 30–90 min, but not the initial mEPSC enhancement.

Methods

  • Primary rat hippocampal and cortical neuron cultures (postnatal day 1–2), Rat2 and HEK293 cells; shRNA lentiviral knockdown, cDNA transfection, cLTP induction with 400 µM glycine in Mg²⁺-free HBS for 5 min, pharmacological inhibitors, live imaging, immunocytochemistry, surface biotinylation, and Western blot.
  • Whole-cell patch-clamp mEPSC recordings; confocal imaging with Manders’ colocalization, spine density/width/type quantification; statistics used t tests, one-way ANOVA with Tukey or Fisher’s LSD, and two-way ANOVA with Sidak, with at least three independent experiments.

Limitations

  • Stated: findings require further testing in vivo; how increased synaptic activity triggers SNX17 recruitment to endosomes remains unclear; sources of synaptic PI(3)P are unknown; the full neuronal SNX17 proteome is not defined; data distribution was assumed normal but not formally tested.
  • Evident from the text: all experiments are in cultured rat neurons or cell lines, with no in vivo electrophysiology, behavior, or disease-model validation; conclusions rely heavily on shRNA knockdown and overexpression/rescue, and cargo specificity is inferred mainly from β1-integrin rather than a complete cargo analysis.

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

Integrity signals

Registry

Crossref · 10.1083/jcb.202207025

Cites

96 of 96 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

32 of 62 cited sources checked · 24 supported · 0 flagged · accuracy not yet measured

  • Interpretationown data

    Given that mushroom spines represent the most mature spine category, the data suggest that SNX17 plays a role in dendritic spine maturation.

    “Given that mushroom spines represent the most mature spine category (Hlushchenko et al., 2016), the data suggest that SNX17 plays a role in dendritic spine maturation.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Hlushchenko et al., 2016 source
  • Premisecitation

    Mutations in subunits of the SNX17-Retriever-CCC-WASH recycling pathway are involved in human pathologies primarily affecting the nervous system.

    “Importantly, a growing body of evidence indicates that mutations in subunits of the SNX17-Retriever-CCC-WASH recycling pathway are involved in human pathologies primarily affecting the nervous system.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Lockstone et al., 2007 source

      The ‘Functional profiling in adult and fetus’ section reports altered gene expression and vesicle-trafficking processes in adult Down syndrome brain, but does not link mutations in SNX17-Retriever-CCC-WASH subunits to nervous-system pathologies. Searches for the pathway names and for mutations in its subunits found no passage addressing that claim. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites Kato et al., 2020 source
    • cites Elliott et al., 2013 source
  • Premisecitation

    Deletion of β1-integrin at postnatal stages impairs LTP.

    “Deletion of β1-integrin at postnatal stages impairs LTP (Huang et al., 2006), and interfering with β1-integrin function prevents the stabilization of LTP (Chun et al., 2001; Kramár et al., 2006).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Huang et al., 2006 source
    • cites Chun et al., 2001 source
    • cites Kramár et al., 2006 source
  • Premisecitation

    Addition of an N-terminal tag to SNX17 does not interfere with its binding to cargo or endosomes.

    “Based on previous studies, the addition of an N-terminal tag to SNX17 does not interfere with its binding to cargo or endosomes (McNally et al., 2017).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites McNally et al., 2017 source
  • Premisecitation

    The L470G mutant of GFP-SNX17 is defective in binding to Retriever.

    “we examined the dynamic localization of an L470G mutant of GFP-SNX17, which is defective in binding to Retriever (McNally et al., 2017).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites McNally et al., 2017 source
  • It may state two separate claims as one. 40
  • Probably not a substantial claim. 36

  • It may state two separate claims as one.

    Premisecitation

    A postnatal forebrain and excitatory neuron-specific knockout of β1-integrin in the mouse showed impaired synaptic transmission through AMPARs as well as decreased NMDAR-dependent LTP.

    “A postnatal forebrain and excitatory neuron-specific knockout of β1-integrin in the mouse showed impaired synaptic transmission through AMPA-type glutamate receptors (AMPARs) as well as decreased N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP), even though the steady-state expression of AMPAR subunits are not regulated by β1-integrin (Chan et al., 2006).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Chan et al., 2006 source

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

    Premisecitation

    Prior to the discovery of the Retriever complex, SNX17 was shown to be present in neurons and regulate the trafficking of proteins including APP, LRP1, and ApoER2.

    “Prior to the discovery of the Retriever complex, SNX17 was shown to be present in neurons and regulate the trafficking of proteins including the amyloid precursor protein (APP; Lee et al., 2008), LRP1 (Donoso et al., 2009), and ApoER2 (Sotelo et al., 2014; Feng et al., 2020).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Lee et al., 2008 source
    • cites Donoso et al., 2009 source
    • cites Sotelo et al., 2014 source

  • Probably not a substantial claim.

    Premisecitation

    In neurons, the surface expression of neurotransmitter receptors, ion channels, and adhesion molecules critical for synaptic function depends on precise endomembrane trafficking mechanisms.

    “In neurons, the surface expression of neurotransmitter receptors, ion channels, and adhesion molecules critical for synaptic function depends on precise endomembrane trafficking mechanisms (Kennedy and Ehlers, 2006; Hiester et al., 2018), and defects in the regulated trafficking of these proteins contribute to neurological disease.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Kennedy and Ehlers, 2006 source
    • cites Hiester et al., 2018 source

      The Introduction sections on AMPA receptors and future directions describe recycling-endosome trafficking of AMPA receptors to the neuronal surface and surface trafficking of adhesion-related proteins, including N-cadherin. The copy does not establish the same dependence for ion channels as a separate class; it also says the full repertoire of synaptic proteins trafficked to the surface remains to be identified. The later statement about neurological disease is outside the clause attributed to this citation. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim.

    Premisecitation

    β1-integrin plays key roles in the regulation of synaptic function and plasticity.

    “Previous studies show that β1-integrin plays key roles in the regulation of synaptic function and plasticity.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites Mortillo et al., 2012 source
    • cites Chan et al., 2006 source
    • cites Huang et al., 2006 source

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

    Premisecitation

    β1-integrin is a well-characterized cargo of SNX17.

    “Among the best-characterized cargoes of SNX17 is the adhesion molecule β1-integrin (Steinberg et al., 2012; Böttcher et al., 2012; McNally et al., 2017).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Steinberg et al., 2012 source
    • cites Böttcher et al., 2012 source
    • cites McNally et al., 2017 source

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

    Premisecitation

    In non-neuronal cells, a major endosomal recycling pathway mediated by SNX17 and the Retriever complex recycles over 120 cell-surface proteins from endosomes to the plasma membrane.

    “In non-neuronal cells, another major endosomal recycling pathway was recently discovered, which mediates the recycling from endosomes to the plasma membrane of over 120 cell-surface proteins, including numerous cell adhesion proteins, signaling receptors, and solute transporters (McNally et al., 2017).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites McNally et al., 2017 source

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

    Premisecitation

    In mouse embryonic fibroblasts, approximately two-thirds of the PI(3)P pool is generated by the lipid kinase VPS34.

    “In mouse embryonic fibroblasts, approximately two-thirds of the PI(3)P pool is generated by the lipid kinase VPS34 (Devereaux et al., 2013; Ikonomov et al., 2015).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Devereaux et al., 2013 source
    • cites Ikonomov et al., 2015 source

      Results §3.4 reports that Vps34 knockout reduced PtdIns3P to about 45% of control levels, but those measurements were in podocytes, not mouse embryonic fibroblasts. Results §3.3 mentions Vps34-knockout fibroblasts only in connection with evidence for additional sources of localized PtdIns3P; it does not quantify their Vps34-generated pool. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    β1-integrin plays key roles in neurite outgrowth, axon guidance, and in the formation and maintenance of synapses.

    “β1-integrin plays key roles in neurite outgrowth, axon guidance, and in the formation and maintenance of synapses (Cheah and Andrews, 2018; Lilja and Ivaska, 2018; Park and Goda, 2016).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Cheah and Andrews, 2018 source

      The ‘Outside–In’ Signalling section links β1-containing integrins to neurite growth, and the Introduction says integrins are required for synaptogenesis. The paper discusses guidance cues in axon regeneration, but does not establish a specific role for β1-integrin in axon guidance or synapse maintenance. No page numbers are available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Lilja and Ivaska, 2018 source
    • cites Park and Goda, 2016 source

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

    Premisecitation

    EEA1 is a marker for early endosomes and extensively colocalizes with SNX17 in an epithelial cell line.

    “EEA1 is a marker for early endosomes and extensively colocalizes with SNX17 in an epithelial cell line (Steinberg et al., 2012).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Steinberg et al., 2012 source

  • It may state two separate claims as one.

    Premisecitation

    VPS35 is a marker of the Retromer complex, and both Retromer and Retriever pathways emerge from the same microdomains of VPS35-containing endosomes.

    “VPS35 is a marker of the Retromer complex, and both Retromer and Retriever pathways emerge from the same microdomains of VPS35-containing endosomes (McNally et al., 2017; Singla et al., 2019).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites McNally et al., 2017 source
    • cites Singla et al., 2019 source

      The Introduction identifies VPS35 as a retromer subunit, supporting its use as a marker. In Results (‘CCC links retriever to WASH-containing endosomal domains’), VPS35L puncta are reported near retromer-containing domains, but the paper does not establish that both pathways emerge from the same microdomains of VPS35-containing endosomes. Page numbers were not provided in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Mutations associated with Ritscher-Schinzel syndrome cause a decrease in the levels of Retriever subunits or CCC subunits, which interferes with the normal function of these complexes.

    “several mutations associated with Ritscher-Schinzel syndrome cause a decrease in the levels of Retriever subunits (Otsuji et al., 2022; Kato et al., 2020) or CCC subunits (Starokadomskyy et al., 2013), which interferes with the normal function of these complexes.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Otsuji et al., 2022 source
    • cites Kato et al., 2020 source
    • cites Starokadomskyy et al., 2013 source

      In “CCDC22 regulates the cellular localization of COMMD proteins” (page not provided), the paper reports a modest decrease in CCDC22 protein in cells from people with the T17A mutation and impaired binding of that protein to COMMD1. It describes the affected family as having XLID and other developmental abnormalities, not Ritscher-Schinzel syndrome, and does not establish reduced levels of CCC subunits generally or test the CCC complex under that name. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    LTP-dependent recycling of AMPARs from intracellular compartments is dependent on the SNX27 pathway.

    “Among the best characterized is the LTP-dependent recycling of AMPARs from intracellular compartments, which is dependent on the SNX27 pathway (Temkin et al., 2017; Loo et al., 2014; Hussain et al., 2014; Wang et al., 2013).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Temkin et al., 2017 source
    • cites Loo et al., 2014 source
    • cites Hussain et al., 2014 source

  • Probably not a substantial claim.

    Premisecitation

    Altered endosomal recycling has been implicated in neurodegenerative diseases, including Alzheimer's and Parkinson's disease.

    “Altered endosomal recycling has been implicated in neurodegenerative diseases, including Alzheimer’s (Small et al., 2005; Small et al., 2017) and Parkinson’s disease (Vilariño-Güell et al., 2011; Zimprich et al., 2011; Zavodszky et al., 2014; McGough et al., 2014).”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Small et al., 2005 source
    • cites Small et al., 2017 source
    • cites Vilariño-Güell et al., 2011 source

  • It may state two separate claims as one.

    Findingown data

    Upon SNX17 knockdown, there was a 65% decrease in the number of mushroom-shaped spines, while filopodia became around 35% more abundant (thin: 56.0 ± 3.8%, mushroom: 6.4 ± 1.1%, filopodium: 27.2 ± 3.5%, stubby: 9.1 ± 2.1%, and flat: 1.3 ± 0.4%).

    “In contrast, upon SNX17 knockdown, there was a striking 65% decrease in the number of mushroom-shaped spines, while filopodia became around 35% more abundant (thin: 56.0 ± 3.8%, mushroom: 6.4 ± 1.1%, filopodium: 27.2 ± 3.5%, stubby: 9.1 ± 2.1%, and flat: 1.3 ± 0.4%; Fig. 2 H).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    SNX17 knockdown causes a reduction in the number of filopodia and a decrease in the number of mushroom spines.

    “Our results show that SNX17 knockdown causes a reduction in the number of filopodia and a decrease in the number of mushroom spines.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    VPS35L and COMMD1 are present in 61.6 ± 10.9% and 62.0 ± 10.3% of excitatory synapses, respectively.

    “VPS35L and COMMD1 are, respectively, present in 61.6 ± 10.9 and 62.0 ± 10.3% of excitatory synapses, defined by the colocalization of PSD95/vGLUT1 (Fig. 1, B and C), and exhibit slightly higher colocalization with each synaptic marker individually (Fig. 1, B, D, and E).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The antibodies used to detect VPS35L and COMMD1 specifically detect their target proteins.

  • It may state two separate claims as one.

    Findingown data

    The number of GFP-SNX17 puncta increases gradually in cLTP-treated neurons but remains constant in mock-treated cells; significant differences first appear at 10 min (1.5-fold increase vs baseline) and become twofold higher at 30 min.

    “The number of GFP-SNX17 puncta increased gradually in cLTP-treated neurons but remained constant in mock-treated cells. Significant differences first appeared at t = 10 min, with a 1.5-fold increase compared with baseline and became twofold higher at t = 30 min (Fig. 7 B).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Spine density was lower in SNX17 knockdown neurons, and this lower spine density remained constant following cLTP.

    “Similarly, while spine density was lower in SNX17 knockdown neurons, this lower spine density remained constant following cLTP (Fig. 3 F).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Dendritic spine density is a valid proxy for the number of excitatory synapses.

  • It may state two separate claims as one.

    Findingown data

    The L470G mutant has similar expression levels to WT and shRNA-resistant GFP-SNX17, exhibits punctate intracellular localization, and maintains colocalization with EEA1.

    “It had similar expression levels to WT and shRNA-resistant GFP-SNX17 (Fig. S3 A), exhibited a punctate intracellular localization, and maintained colocalization with EEA1 (Fig. S3 D).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    VPS34-INH treatment significantly reduces the number of PI(3)P puncta and blocks the cLTP-dependent increase in PI(3)P puncta at 10 min.

    “VPS34-INH treatment caused a significant reduction in the number of PI(3)P puncta and also blocked the cLTP-dependent increase in PI(3)P puncta at 10 min.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: VPS34-INH specifically inhibits VPS34.

  • It may state two separate claims as one.

    Findingown data

    cLTP stimulation induces transient recruitment of SNX17 to excitatory synapses, with maximum colocalization at 10 min after cLTP.

    “The percentage of excitatory synapses that colocalize with SNX17 at the different time points was determined using Mander’s colocalization coefficient (×100). Baseline: 43.310 ± 1.881, N = 43; 10 min after cLTP: 51.750 ± 1.520, N = 42; 30 min after cLTP: 49.930 ± 1.533, N = 43; 60 min after cLTP: 39.680 ± 1.625, N = 43.”
    • Also stated in: § SNX17 is recruited to excitatory synapses during cLTP, and this recruitment is dependent on neuron-specific CaMKII signaling · plain
      “cLTP stimulation induces transient recruitment of SNX17 and other SNX17-Retriever pathway subunits to excitatory synapses”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    In live-cell imaging, cLTP induces maximum GFP-SNX17 recruitment to dendritic spines at 10 min (31.6 ± 0.05% increase vs baseline) and GFP-SNX17 intensity remains significantly elevated up to 30 min after cLTP.

    “Similar to endogenous SNX17 (Fig. 4 B), we observed maximum recruitment to synapses 10 min following cLTP induction, with a 31.6 ± 0.05% increase in GFP-SNX17 intensity at dendritic spines as compared with baseline intensity. GFP-SNX17 intensity at dendritic spines remained significantly elevated during the remaining time points analyzed, up to 30 min after the cLTP stimulus (Fig. 5 C).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    shRNA-resistant GFP-SNX17 fully rescues cLTP-induced changes in spine head width to levels similar to controls, whereas shRNA-resistant L470G GFP-SNX17 does not significantly rescue.

    “Indeed, shRNA-resistant GFP-SNX17 fully rescued cLTP-induced changes in spine head width to levels similar to controls; however there was no significant rescue by shRNA-resistant L470G GFP-SNX17 (Fig. 6 D).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    After 10 min of cLTP, colocalization of SNX17 with VPS35 increases, with no change in colocalization with EEA1.

    “Intriguingly, after 10 min of a cLTP stimulus, we found an increase in the colocalization of SNX17 with VPS35 (Fig. 7, E and F) with no changes in the colocalization with EEA1 (Fig. S4, E and F).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    CaMKII inhibition with AIP blocks cLTP-induced SNX17 recruitment to synapses, whereas PKA inhibition with KT5720 and ERK inhibition with U0126 do not.

    “We found that autocamtide-2-related inhibitory peptide (AIP), a selective and potent inhibitor of CaMKII (Ishida et al., 1995), blocked SNX17 recruitment to synapses upon cLTP stimulation. However, both KT5720 and U0126, which inhibit PKA- and ERK- dependent signaling pathways, respectively, failed to block cLTP-dependent SNX17 recruitment (Fig. 4 E).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ishida et al., 1995 source
    • Rests on an assumption: KT5720 specifically inhibits PKA and U0126 specifically inhibits ERK.

  • It may state two separate claims as one.

    Findingown data

    Chelating intracellular calcium with BAPTA-AM or blocking NMDA receptors with D-APV blocks the cLTP-dependent increase in SNX17 localization to excitatory synapses, whereas blocking L-type VDCCs with nifedipine does not.

    “BAPTA-AM and D-APV treatment completely blocked the cLTP-dependent increase in SNX17 localization to excitatory synapses. Surprisingly, despite the fact that VDCCs are responsible for around 80% of the total calcium entry in response to presynaptic glutamate release (Schiller et al., 1998), nifedipine treatment had no effect on SNX17 recruitment (Fig. 4 D).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    The interaction of SNX17 with Retriever is necessary for the cLTP-dependent recruitment of SNX17 to synapses and for the increase in SNX17-positive puncta.

    “the interaction of SNX17 with Retriever is necessary for the cLTP-dependent recruitment of SNX17 to synapses, as well as for the increase in SNX17-positive puncta.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Synaptic activity engages SNX17-dependent recycling through recruitment of SNX17 and the Retriever complex to synaptic sites, driven by NMDA receptor activation, CaMKII-dependent signaling, and endosomal PI(3)P.

    “We found that synaptic activity engages SNX17-dependent recycling through the recruitment of SNX17 and the Retriever complex to synaptic sites, a process driven by NMDA receptor activation, CaMKII-dependent signaling, and endosomal PI(3)P.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.

    Findingnone given

    Endosomal PI(3)P increases upon cLTP and may help with the recruitment of SNX17 to synapses.

    “Endosomal PI(3)P increases upon cLTP and may help with the recruitment of SNX17 to synapses.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingcitation

    CaMKII activation is necessary and sufficient to promote the recruitment of SNX17 and the Retriever complex to dendritic spines.

    “CaMKII activation is necessary and sufficient to promote the recruitment of SNX17 and the Retriever complex to dendritic spines (3)”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Together, these data suggest that the SNX17-Retriever recycling pathway regulates the density and maturation of excitatory synapses in hippocampal neurons.

    “Together, these data suggest that the SNX17-Retriever recycling pathway regulates the density and maturation of excitatory synapses in hippocampal neurons.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Dendritic spine density is a valid proxy for the number of excitatory synapses.

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

    Premisenone given

    How β1-integrin recycling is regulated in neurons and whether this regulation is coupled to synaptic activity has not been directly tested.

    “However, how β1-integrin recycling is regulated in neurons and importantly whether this regulation is coupled to synaptic activity has not been directly tested.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    β1-integrin localizes to synapses in CA1 hippocampal neurons and is concentrated at the postsynaptic membrane.

    “For example, immunogold labeling showed that β1-integrin localizes to synapses in CA1 hippocampal neurons and is concentrated at the postsynaptic membrane (Mortillo et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mortillo et al., 2012 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim.

    Premisenone given

    The roles and regulation of SNX17 and Retriever at synaptic sites have not been directly tested.

    “However, the roles and the regulation of SNX17 and the Retriever at synaptic sites have not been directly tested.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    SNX17-dependent recycling requires the WASH complex and the CCC complex.

    “In addition, SNX17-dependent recycling requires the WASH complex and the CCC complex, which includes coiled-coil domain containing 22 (CCDC22), coiled-coil domain containing 93 (CCDC93), and 10 copper metabolism MURR1 domain (COMMD)-containing proteins (Chen et al., 2019; McNally and Cullen, 2018; Simonetti and Cullen, 2019; Wang et al., 2018a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chen et al., 2019 source
    • cites McNally and Cullen, 2018

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

    • cites Simonetti and Cullen, 2019

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

  • It may state two separate claims as one.

    Interpretationown data

    The abundance of SNX17 and other proteins of the recycling pathway at synapses suggests that SNX17-dependent recycling may play a role in regulating synaptic function.

    “The abundance of SNX17 and other proteins of the recycling pathway at synapses suggests that SNX17-dependent recycling may play a role in regulating synaptic function.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationreasoning

    Recycling of SNX17-dependent cargoes plays a role in the functional and/or structural plasticity necessary for LTP.

    “That the SNX17 pathway is actively engaged after cLTP suggests that the recycling of SNX17-dependent cargoes plays a role in the functional and/or structural plasticity necessary for LTP.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    Retriever binding to SNX17 is necessary for SNX17 recruitment to synapses and for cLTP-dependent changes at synapses that occur downstream of SNX17 recruitment.

    “These studies indicate that Retriever binding to SNX17 is necessary for SNX17 recruitment to synapses as well as for cLTP-dependent changes at synapses that occur downstream of SNX17 recruitment.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    CaMKII-T286D induces LTP when introduced with a viral expression system or by direct injection into postsynaptic cells.

    “This mutant induces LTP when introduced with a viral expression system (Pettit et al., 1994) or by direct injection into postsynaptic cells (Lledo et al., 1995).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Pettit et al., 1994 source
    • cites Lledo et al., 1995 source

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

    Premisecitation

    During LTP, many signaling enzymes are activated, including CaMKII, PKA, and ERK.

    “During LTP, many signaling enzymes are activated including calcium/calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA), and Ras-extracellular signal-regulated kinase (ERK; Lisman et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lisman et al., 2012 source

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

    Premisecitation

    cLTP requires NMDA receptor activation, which results in increased postsynaptic calcium and activation of downstream signaling cascades that increase synaptic efficacy.

    “cLTP requires N-methyl-D-aspartate (NMDA) receptor activation, which results in an increase in postsynaptic calcium and the activation of several downstream signaling cascades, which in turn result in an increase in synaptic efficacy (Musleh et al., 1997).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Musleh et al., 1997 source

      Checked before — its earlier verdict is held back until a new check runs.

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

    Premisecitation

    In HeLa cells, many adhesion molecules, signaling receptors, and solute transporters recycle via the SNX17-Retriever pathway.

    “In HeLa cells, many adhesion molecules, signaling receptors, and solute transporters recycle via the SNX17-Retriever pathway (McNally et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites McNally et al., 2017 source

  • Probably not a substantial claim.

    Premisecitation

    VPS34 regulates SNX17 recruitment to endosomes in HeLa cells.

    “We previously showed that VPS34 regulates SNX17 recruitment to endosomes in HeLa cells (Giridharan et al., 2022).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Giridharan et al., 2022 source

      Checked before — its earlier verdict is held back until a new check runs.

  • Probably not a substantial claim.

    Premisecitation

    dsRed-EEA1-FYVE potently and specifically binds PI(3)P.

    “We transfected rat hippocampal neurons with dsRed-EEA1-FYVE, a bioprobe that potently and specifically binds PI(3)P (Singla et al., 2019).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Singla et al., 2019 source

  • It may state two separate claims as one.

    Interpretationown data

    cLTP stimulation induces transient recruitment of SNX17 and other SNX17-Retriever pathway subunits to excitatory synapses, and activity-dependent CaMKII signaling is upstream of this SNX17 recruitment.

    “Together, our results indicate that cLTP stimulation induces transient recruitment of SNX17 and other SNX17-Retriever pathway subunits to excitatory synapses and that activity-dependent CaMKII-signaling is upstream of this SNX17-recruitment.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    SNX17 is actively recruited to synapses during cLTP, and this recruitment is specifically related to the structural enlargement of spines necessary for enduring increases in synaptic function.

    “These results indicate that SNX17 is actively recruited to synapses during cLTP, and this recruitment is specifically related to the structural enlargement of spines necessary for enduring increases in synaptic function.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    AIP is a selective and potent inhibitor of CaMKII.

    “autocamtide-2-related inhibitory peptide (AIP), a selective and potent inhibitor of CaMKII (Ishida et al., 1995)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ishida et al., 1995 source

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

    Study design and conductnone given

    All experimental protocols were approved by the University of Michigan Committee on the Use and Care of Animals.

    “All experimental protocols were approved by the University of Michigan Committee on the Use and Care of Animals.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All experiments were repeated at least three times.

    “All experiments were repeated at least three times.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Equal amounts of protein were loaded into gels for Western blot analysis.

    “Protein concentrations were determined using a commercial BCA assay (Pierce), and equal amounts of protein were loaded into Mini-PROTEAN TGX Precast gels (Bio-Rad) and transferred to nitrocellulose membranes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.

    Interpretationreasoning

    The SNX17-Retriever pathway may provide a novel therapeutic target for Alzheimer's disease and related neurodegenerative disorders.

    “Similarly, the SNX17-Retriever pathway may also provide a novel therapeutic target for Alzheimer’s disease and related neurodegenerative disorders.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The identity of the constructs was verified by sequencing the entire coding region.

    “In all cases, the identity of the constructs was verified by sequencing the entire coding region.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationown data

    SNX17-dependent recycling is also engaged during LTP, which likely plays a key role in activity-dependent changes in the surface proteome.

    “Our data reveal that SNX17-dependent recycling is also engaged during LTP, which likely also plays a key role in activity-dependent changes in the surface proteome.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    The SNX17-Retriever recycling pathway is localized to excitatory synapses and is actively engaged during long-lasting forms of synaptic plasticity.

    “The studies reported here reveal that the SNX17-Retriever recycling pathway is localized to excitatory synapses and is actively engaged during long-lasting forms of synaptic plasticity.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Single excitation for each wavelength separately was used for all acquisitions.

    “Single excitation for each wavelength separately was used for all acquisitions.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    SNX17 may contribute to altered receptor recycling in neurodegeneration.

    “The critical roles of SNX17 in neurons open the possibility that it may contribute to altered receptor recycling in neurodegeneration.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    To prepare representative images, brightness and contrast were adjusted uniformly over all images of the respective assays.

    “To prepare representative images, the brightness and contrast were adjusted uniformly over all images of the respective assays using Photoshop 2021.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All solutions were prechilled to 4°C and all steps were carried out in ice to prevent internalization of surface β1-integrin.

    “All solutions were prechilled to 4°C and all steps were carried out in ice to prevent internalization of surface β1-integrin.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Interpretationown data

    SNX17-dependent recycling is critical to maintain dendritic spine density and for the structural changes in dendritic spines associated with cLTP.

    “Taken together, these studies demonstrate that SNX17-dependent recycling is critical to maintain dendritic spine density and for the structural changes in dendritic spines that are associated with cLTP.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim.

    Premisecitation

    Upregulating the SNX27-Retromer pathway has shown therapeutic potential for Alzheimer's disease.

    “upregulating the SNX27-Retromer pathway has shown therapeutic potential for Alzheimer’s disease (Li et al., 2020).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Li et al., 2020

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

  • It may state two separate claims as one.

    Interpretationcitation

    Surface levels of β1-integrin increase during cLTP and promote dendritic spine growth.

    “The surface levels of β1-integrin increase during cLTP and promote dendritic spine growth (5).”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Cells were tested for mycoplasma using LookOut Mycoplasma PCR Detection Kit.

    “Cells were tested for mycoplasma using LookOut Mycoplasma PCR Detection Kit (Sigma-Aldrich).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The same laser settings and exposure times were used for the acquisition of individual experiments.

    “The same laser settings and exposure times were used for the acquisition of individual experiments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim.

    Study design and conductown data

    SNX17 knockdown was validated by Western blot of the lysate.

    “SNX17 knockdown was validated by Western blot of the lysate and GAPDH was used as a loading control.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Dendritic spine numbers and morphology were quantified manually by an observer blind to the experimental conditions.

    “Dendritic spine numbers and morphology were quantified manually by an observer blind to the experimental conditions 30 or 50 μm segments, as indicated, of dendrites after the first dendritic branchpoint.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Interpretationreasoning

    The SNX17-Retriever pathway is required for dendritic spine maintenance and the cLTP-dependent increase in dendritic spine size.

    “The SNX17-Retriever pathway is required for dendritic spine maintenance and the cLTP-dependent increase in dendritic spine size.”
    Quote in the paperSubstantial claim
66 of 66

  • The paper relies on this without support.

    Dendritic spine density is a valid proxy for the number of excitatory synapses.

    “a structural hallmark of excitatory synaptic contacts”

  • The paper relies on this without support.

    The antibodies used to detect VPS35L and COMMD1 specifically detect their target proteins.

    “VPS35L and COMMD1 are, respectively, present in 61.6 ± 10.9 and 62.0 ± 10.3% of excitatory synapses, defined by the colocalization of PSD95/vGLUT1”

  • The paper relies on this without support.

    KT5720 specifically inhibits PKA and U0126 specifically inhibits ERK.

    “both KT5720 and U0126, which inhibit PKA- and ERK- dependent signaling pathways, respectively”

  • The paper relies on this without support.

    VPS34-INH specifically inhibits VPS34.

    “we transiently transfected neurons with dsRed-EEA1-FYVE and GFP-SNX17 and analyzed the numbers of PI(3)P puncta and GFP-SNX17 puncta at 10 and 30 min following cLTP in the presence or absence of VPS34 inhibitor (VPS34-INH).”

  • The paper relies on this without support.

    SNX17 shRNA specifically reduces SNX17 levels.

    “we transduced neurons with lentiviruses carrying an shRNA targeting SNX17 or a scrambled control shRNA and performed surface biotinylation assays.”

  • The paper relies on this without support.

    In neurons, most cargos that traffic via SNX17-Retriever have not yet been identified.

    “However, in neurons, most cargos that traffic via SNX17-Retriever have not yet been identified.”

  • The authors state this as an assumption.

    The data distribution was assumed to be normal, but this was not formally tested.

    “Data distribution was assumed to be normal, but this was not formally tested.”
7 of 7

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?

  • Blocking β1-integrin disrupts cLTP induction.

    “we confirmed that blocking β1-integrin similarly disrupts cLTP induction (Rivero Rios et al., 2023).”

    From Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity (2025) · cites this paper as Rivero Rios et al., 2023

    The Results section (“Blocking β1-integrin function mimics most effects of SNX17 knockdown on synaptic function,” Fig. 9) says β1-integrin blocking did not alter the initial cLTP-dependent enhancement during the first 30 minutes. It disrupted maintenance after 30 minutes, whereas SNX17 knockdown blocked initiation. The source therefore contradicts the claim about cLTP induction. (LLM, conf=0.94)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • LTP stimulation recruits SNX17 to synaptic sites, and SNX17-dependent recycling of β1-integrin via Retriever is necessary for LTP.

    “A similar instructive role for SNX17-Retriever can be inferred: LTP stimulation recruits SNX17 to synaptic sites, and SNX17-dependent recycling of β1-integrin via Retriever is necessary for LTP (Rivero-Rios et al., 2023).”

    From Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity (2025) · cites this paper as Rivero-Rios et al., 2023

    The Discussion reports that cLTP recruits SNX17 and Retriever to synaptic sites. The Results show that SNX17 controls activity-dependent surface β1-integrin levels, but β1-integrin blockade disrupts maintenance—not initiation—of cLTP; the authors say other SNX17 cargoes may be required for initiation. Thus, saying β1-integrin recycling is necessary for LTP without that distinction overstates its demonstrated role. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In vivo SNX17 knockdown in developing rat CA1 reduces synapse density 2 weeks post-surgery.

    “Similar to Rivero Rios et al. (2023), we observed a marked reduction in synapse density in CA1 pyramidal neurons 2 weeks post-surgery (P22–24).”

    From Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity (2025) · cites this paper as Rivero Rios et al., 2023

    The Results (Figure 2; page unavailable) report reduced dendritic spine density after SNX17 knockdown in cultured rat hippocampal neurons. The paper does not establish the attributed in vivo finding in developing rat CA1 neurons two weeks after surgery; its cultured neurons were assessed four days after transfection. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • β1-integrin is a key SNX17 cargo in hippocampal neurons, and its recycling is required for long-term potentiation of synapse strength.

    “Recent work has identified β1-integrin as a key SNX17 cargo in hippocampal neurons, where its recycling is required for long-term potentiation of synapse strength”

    From Dual endomembrane recycling pathways function in parallel to support synapse maintenance and plasticity (2025) · cites this paper as Rivero-Ríos et al., 2023

    The Results section identifies β1-integrin as an SNX17 cargo in neurons and reports that SNX17 knockdown prevents its cLTP-associated increase at the surface of hippocampal neurons. Blocking β1-integrin disrupted maintenance of potentiated synaptic strength, but the paper did not directly test whether β1-integrin recycling itself is required for that maintenance; it also found that SNX17 knockdown and β1-integrin blockade affect different phases of cLTP. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • In neurons, the SNX17-Retriever pathway plays a key role in regulating synapse function and plasticity.

    “in neurons, this pathway also plays a key role in regulating synapse function and plasticity”

    From PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity (2025) · cites this paper as Rivero-Ríos et al., 2023

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.

  • Figure S3E names wild-type SNX17 while the text cites it for the L470G mutant

    Minor

    The text cites Figure S3E as showing that L470G fails to colocalize with PSD95, but the legend says those neurons were transfected with GFP-SNX17, not GFP-SNX17-R-L470G.

  • Late β1-integrin recording interval is stated as both 30-60 and 30-90 minutes

    Minor

    The results text places the disrupted maintenance of cLTP at 30-60 min, but the Figure 9 legend defines the corresponding late recordings as 30-90 min after cLTP.

  • Figure 7 puncta counts are described as baseline-normalized but have nonunit baselines

    Minor

    Normalization to the baseline for each dendrite would make the reported baseline equal to 1.000. Instead, Figure 7B gives baseline values of 0.219 and 0.231; Figure 7D makes the same normalization claim and also reports nonunit baselines.

  • VPS34 inhibitor pretreatment duration differs between methods and figure

    Minor

    Figure S5 specifies 15 min of VPS34-INH pretreatment, while the cLTP methods list VPS34-INH among compounds for which neurons were pretreated for 30 min.

4 of 4

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1038/s41380-019-0364-x

    Major

    The cited work was retracted on 2022-10-18 (notice 10.1038/s41380-022-01814-1), before this paper was published (2023-05-04). Its authors could have known.

    Cited work 10.1038/s41380-019-0364-x · retracted 2022-10-18 · notice 10.1038/s41380-022-01814-1 · this paper published 2023-05-04

1 of 1

Citations

Cites

1 retracted

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Metadata

Authors
Rivero-Ríos, P., Tsukahara, T., Uygun, T., Chen, A., Chavis, G. D., Giridharan, S. S. P., Iwase, S., Sutton, M. A., & Weisman, L. S.
Affiliations
University of Michigan (US)
Corresponding author
  • Sutton, Michael A.
  • Weisman, Lois S.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2023-05-04
Volume
222
Issue
7
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.202207025
PMC
PMC10165670
OpenAlex
W4368356085
Cited by
17
References
96
Citations by year
2026: 3 · 2025: 9 · 2024: 5
FWCI
1.71
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01-NS129198, R01-NS099340, R01-NS064015, R01-NS097498, R21-NS125449, R01-NS116008)
  • University of Michigan
  • National Institute on Aging (P30AG072931)
  • National Institutes of Health (18-PAF03228)
  • University of Michigan Alzheimer’s Disease Center
  • National Institute of Mental Health (R21-MH127485)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
SNX17, Retriever, WASH complex, endosomal recycling, synaptic plasticity, long-term potentiation, beta1 integrin, NMDA receptor, CaMKII signaling, phosphatidylinositol 3-phosphate, excitatory synapses, hippocampal neurons, synapse maintenance
MeSH terms
Cell Membrane, Cells, Cultured, Membrane Proteins, Neuronal Plasticity, Neurons, Synapses, Long-Term Potentiation, Phosphatidylinositol Phosphates, Protein Transport, Sorting Nexins

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 2026-11-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-08 (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.

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