The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning

Classified as probably not a substantial claim.

Spine motility permits the sampling of large numbers of potential presynaptic partners before connections are stabilized via activity-dependent mechanisms.

“This would be advantageous, because spine motility permits the sampling of large numbers of potential presynaptic partners before connections are stabilized via activity-dependent mechanisms (Jontes and Smith, 2000; Portera-Cailliau et al., 2003).”

• cites Jontes and Smith, 2000 sourceDisputed

  In the discussion of divergent roles for filopodia and spines (page unavailable), the paper assigns broad sampling of potential inputs to motile filopodia. It says new spines instead appear preferentially associated with previously active presynaptic boutons, strengthening an existing connection—not sampling many potential partners. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites Portera-Cailliau et al., 2003 sourcePartly supported

  The Introduction says spines are motile, and the discussion section 'Shaft filopodia: a role in synaptogenesis or spinogenesis' proposes that motile shaft filopodia seek suitable synaptic partners and that dendritic protrusions stabilize as activity increases. But the proposed partner-search mechanism concerns filopodia rather than spines; the paper does not establish that spine motility samples large numbers of partners before connections stabilize. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

IDOL and LXR signaling regulate lipoprotein receptors in a cell type-specific manner.

“since IDOL and LXR signaling regulate lipoprotein receptors in a cell type-specific manner (Hong et al., 2014)”

• cites Hong et al., 2014 sourceSupported

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

PSD95 and NR1 rise due to the robust synaptogenesis that occurs during this time.

“which rise due to the robust synaptogenesis that occurs during this time (Sans et al., 2000).”

• cites Sans et al., 2000 sourcePartly supported

  The Results section (‘Development of PSD-95/SAP-102 proteins at the synapse’; page unavailable) reports that synaptic PSD-95 increases during development. The Discussion attributes this mainly to more synapses containing PSD-95, not to demonstrated synaptogenesis; it treats formation of new synapses as an alternative explanation. The cited passages do not establish a developmental rise in NR1. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

Synaptic plasticity and learning are associated with changes in spine morphology.

“mounting evidence indicates that synaptic plasticity and learning are associated with changes in spine morphology”

• cites Gambino et al., 2014 sourceNot checked — no full text of the source
• cites Hayashi-Takagi et al., 2015 sourceSupported

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

IDOL is an E3 ubiquitin ligase whose expression is transcriptionally controlled by liver X receptors in cell types such as hepatocytes and macrophages.

“Inducible Degrader of the LDL receptor (IDOL; encoded by the Mylip gene), an E3 ubiquitin ligase whose expression is transcriptionally controlled by liver X receptors in (LXRs) in cell types such as hepatocytes and macrophages (Zelcer et al., 2009).”

• cites Zelcer et al., 2009 sourceSupported

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

Spine morphological changes depend on NMDAR activation.

“and that these morphological changes depend on NMDAR activation (Gambino et al., 2014; Hayashi-Takagi et al., 2015)”

• cites Gambino et al., 2014 sourceNot checked — no full text of the source
• cites Hayashi-Takagi et al., 2015 sourceCould not verify

  The ‘Selective spine shrinkage by AS-PaRac1’ section attributes the observed shrinkage to photoactivated Rac1, but does not test whether it depends on NMDAR activation. A search for NMDAR activation and NMDA receptor blockade found receptor-related references, but no passage in our copy establishes the claimed dependence of spine morphological changes. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

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

The IDOL-UBE2D complex ubiquitinates the LDLR on its cytoplasmic domain, thereby targeting it for lysosomal degradation.

“The IDOL-UBE2D complex ubiquitinates the LDLR on its cytoplasmic domain, thereby targeting it for lysosomal degradation (Zhang et al., 2011).”

• cites Zhang et al., 2011 sourcePartly supported

  The section “UBE2D family proteins are the E2 enzymes for LDLR ubiquitination” reports that LDLR is ubiquitinated in the presence of IDOL and UBE2D2, and that bafilomycin blocks IDOL-dependent LDLR degradation, supporting a lysosomal pathway. Our copy does not establish that the ubiquitination occurs specifically on LDLR’s cytoplasmic domain. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Alteration of dendritic spine morphology and density in response to neuronal activity is a vital component of neural plasticity.

“Alteration of dendritic spine morphology and density in response to neuronal activity is a vital component of neural plasticity (Hotulainen and Hoogenraad, 2010).”

• cites Hotulainen and Hoogenraad, 2010 sourcePartly supported

  The Introduction’s “Dendritic spine structure and function” section says neuronal activity can alter spine morphology and links spine-head enlargement to LTP. The Introduction also links spine appearance and disappearance—which can change density—to learning and memory, but our copy does not clearly say that neuronal activity alters spine density. (LLM, conf=0.80)

  Experimental — accuracy not yet measured

May combine two claims.

Mice lacking ApoER2 display a defect in LTP while exhibiting normal baseline synaptic transmission.

“Mice lacking ApoER2 display a defect in LTP while exhibiting normal baseline synaptic transmission (Weeber et al., 2002)”

• cites Weeber et al., 2002 sourceSupported

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

The LXR-IDOL pathway regulates cellular cholesterol levels and impacts plasma LDL levels in primates.

“Prior studies have shown that the LXR-IDOL pathway regulates cellular cholesterol levels and impacts plasma LDL levels in primates (Hong et al., 2014; Scotti et al., 2011).”

• cites Hong et al., 2014 sourceSupported
• cites Scotti et al., 2011 sourcePartly supported

  The Results and Discussion report that the LXR-IDOL pathway regulates LDL receptor levels and LDL uptake in mouse embryonic stem cells, supporting its role in cellular cholesterol regulation. The paper does not report an effect on plasma LDL levels in primates; its discussion of raised plasma LDL concerns mice, not primates. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Tiam1 is the major Rac guanine nucleotide exchange factor that couples NMDAR to Rac1.

“It has previously been reported that c-jun-terminal kinase interacting proteins 1/2 (JIP1/2) interact with ApoER2 (Stockinger et al., 2000) as well as Tiam1 (Buchsbaum et al., 2002), the major Rac guanine nucleotide exchange factor that couples the NMDAR to Rac1 (Tolias et al., 2005).”

• cites Tolias et al., 2005 sourcePartly supported

  The Introduction (p. 1) identifies Tiam1 as a Rac1-specific GEF, and the Discussion (p. 10) says it activates Rac1 in response to NMDA receptor stimulation. The paper does not establish that Tiam1 is the *major* GEF coupling the receptor to Rac1; it also says the precise coupling mechanism remains to be determined (Discussion, p. 9). (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

IDOL promotes the degradation of ApoER2 and VLDLR in cultured cells.

“Studies in cultured cells have shown that IDOL also promotes the degradation of ApoER2 and VLDLR (Hong et al., 2010)”

• cites Hong et al., 2010 sourceSupported

Classified as probably not a substantial claim.

Mild increases in ApoER2 levels in response to exon 16 deletion led to enhanced LTP.

“Interestingly, while mild increases in ApoER2 levels in response to exon 16 deletion led to enhanced LTP (Wasser et al., 2014), we showed constitutive high level of ApoER2 expression in IDOL-deficient mice severely impaired LTP.”

• cites Wasser et al., 2014 sourcePartly supported

  The Results report that exon 16 deletion increased Apoer2 abundance and enhanced LTP in hippocampal slices when exon 19 was present. But deletion of exon 16 did not enhance LTP when exon 19 was also absent, so the claim omits a necessary condition. The Results describe a twofold Apoer2 increase in the mice with enhanced LTP, rather than characterizing it as mild. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Lrp8 lacking exon 16 increases the stability of ApoER2 in neurons and is associated with higher spine density.

“Lrp8 lacking exon 16, which encodes the O-linked sugar (OLS) domain, increased the stability of ApoER2 in neurons and was associated with higher spine density (Wasser et al., 2014).”

• cites Wasser et al., 2014 sourcePartly supported

  The Results section on hippocampal spine density reports increased Apoer2 abundance in exon-16-lacking mice and higher spine density, though the increase in average spine density was significant only in mice also lacking exon 19 (page unavailable). The Discussion says reduced cleavage might make Apoer2 more stable, but also reports increased Apoer2 mRNA; it does not establish increased protein stability in neurons as a measured finding. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

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

Tiam1 is a Rac-GEF implicated in activity-dependent remodeling of dendritic arbors and is responsible for coupling between NMDAR and Rac1.

“One Rac-GEF implicated in the activity-dependent remodeling of dendritic arbors is Tiam1, which is responsible for the coupling between NMDAR and Rac1 (Tolias et al., 2005).”

• cites Tolias et al., 2005 sourceSupported

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

Postsynaptic JIP and Tiam1 could be involved in mediating the effects of IDOL-ApoER2 axis on Rac1 activity.

“Our data suggest that postsynaptic JIP (Stockinger et al., 2000; Verhey et al., 2001) and Tiam1 (Buchsbaum et al., 2002) could be involved in mediating the effects of IDOL-ApoER2 axis on Rac1 activity.”

• cites Stockinger et al., 2000 sourceNot checked — no full text of the source
• cites Verhey et al., 2001 sourcePartly supported

  The Results section ('Direct Interaction of KLC and the JIP Proteins'; page unavailable) says JIPs are enriched at synaptic junctions and that JIP-1 and JIP-2 interact with ApoER2. It does not establish that JIP is specifically postsynaptic. The proposed IDOL–ApoER2–Rac1 mechanism is framed as the citing authors’ suggestion, not as a finding of this source. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites Buchsbaum et al., 2002 sourceNot checked — no full text of the source

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

JIP is localized at post-synaptic densities (PSD) in neurons and is indispensable for normal function of NMDA receptors.

“Recent studies have shown that JIP is localized at post-synaptic densities (PSD) in neurons, and is indispensable for the normal function of NMDA receptors (Kennedy et al., 2007; Pellet et al., 2000).”

• cites Kennedy et al., 2007 sourceSupported
• cites Pellet et al., 2000 sourceNot checked — no full text of the source

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

Spine density is decreased in ApoER2 KO mice and increased with ApoER2 overexpression.

“Our observation that IDOL bidirectionally regulate spine density through ApoER2 is consistent with previous studies showing that spine density is decreased in ApoER2 KO mice and increased in the setting of ApoER2 overexpression (Dumanis et al., 2011; Wasser et al., 2014).”

• cites Dumanis et al., 2011 sourcePartly supported

  The Results report reduced spine density in ApoEr2 knockout mice at one month of age and increased spine density after ApoEr2 overexpression in cultured hippocampal neurons. The claim omits those conditions: the Results also report no significant spine-density difference between knockout and wild-type mice at one year of age. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites Wasser et al., 2014 sourceSupported

Classified as probably not a substantial claim.

ApoER2 mediates Reelin signaling to enhance learning and memory in mice.

“Since loss of ApoER2 impairs LTP, and since ApoER2 mediates Reelin signaling to enhance learning and memory in mice (Bosch et al., 2016; Niu et al., 2008; Rogers et al., 2011), it has been suggested that increased ApoER2 expression would be beneficial.”

• cites Bosch et al., 2016 sourcePartly supported

  The Introduction states that ApoER2 mediates Reelin signaling. The Discussion reports changes in mouse synapses and suggests that altered Reelin signaling may affect rhythms important for learning and memory, but it does not show that ApoER2-mediated signaling enhances learning or memory in mice. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Niu et al., 2008 sourceSupported
• cites Rogers et al., 2011 sourcePartly supported

  The Results show that Reelin did not increase Dab1 or CREB activation in ApoER2-knockout mice, and the Discussion describes the in vivo signaling as ApoER2-dependent. The paper also reports enhanced learning and memory after Reelin injection in wild-type mice, but does not show that ApoER2 is required for that behavioral improvement. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim. May combine two claims.

Hebbian plasticity, including LTP and LTD, provoke positive feedback responses and are potentially prone to instability.

“Hebbian plasticity, including LTP and LTD, provoke positive feedback responses and are potentially prone to instability (Turrigiano, 2008; Vitureira and Goda, 2013).”

• cites Turrigiano, 2008 sourceSupported
• cites Vitureira and Goda, 2013 sourceSupported

May combine two claims.

IDOL regulates dendritic spine morphogenesis and plasticity.

“Here we demonstrate that the E3 ubiquitin ligase IDOL determines synaptic ApoER2 protein levels in response to neuronal activation and regulates dendritic spine morphogenesis and plasticity.”

May combine two claims.

In mature DIV18 neurons, GFP-IDOL concentrates at synapses and is juxtaposed with the glutamatergic presynaptic marker vGlut1.

“However, in mature DIV18 neurons, GFP-IDOL concentrated at synapses, and was juxtaposed with the glutamatergic presynaptic marker vGlut1 (Figure 1G, Figure 1—figure supplement 2A).”

May combine two claims.

Deletion of IDOL in Mylipflox/flox neurons by AAV-CamKII-Cre results in >95% reduction in mRNA encoding IDOL and strong increases in ApoER2, VLDLR and LDLR protein compared to GFP-expressing AAV.

“Deletion of IDOL in Mylipflox/flox neurons by means of an AAV-CamKII-Cre vector resulted in >95% reduction in mRNA encoding IDOL and strong increases in ApoER2, VLDLR and LDLR protein compared to cells transduced with GFP-expressing AAV vector (Figure 1E, Figure 1—figure supplement 1C).”

May combine two claims.

Neurons overexpressing ApoER2 show increased basal Rac1 activity and compromised Rac1 induction upon Bic treatment, resembling IDOL-deficient neurons.

“Supporting the notion that ApoER2 is the principle mediator of IDOL effects on Rac1, the Rac1 activity phenotype of neurons overexpressing ApoER2 resembled that of IDOL-deficient neurons (Figure 5—figure supplement 1A): both showed increased basal Rac1 activity and compromised Rac1 induction upon Bic treatment.”

May combine two claims.

In IDOL-deficient neurons, spine density is increased by 42%, while spine head width is decreased approximately 50%.

“Spine density was increased by 42%, while spine head width decreased approximately 50% (Figure 4A).”

May combine two claims.

IDOL-deficient mice have higher spine density but reduced head width compared with their WT counterparts in CA1 pyramidal neurons.

“Consistent with results from primary neuron cultures, IDOL-deficient mice had higher spine density but reduced head width compared with their WT counterparts (Figure 4D).”

May combine two claims.

There was a +50% change in map size from baseline in WT compared to no change in IDOL-deficient mice.

“We found a + 50% change in map size from baseline in WT compared to no change in IDOL-deficient mice (Figure 7D).”

May combine two claims.

In WT neurons, Tiam1 is enriched within spine heads, but in IDOL-deficient neurons it is mislocalized to the base of spines.

“In WT neurons Tiam1 was enriched within the spine heads as expected, but it was mislocalized to the base of the spines in IDOL-deficient neurons.”

May combine two claims.

ApoER2 overexpression results in a 2-fold increase in spine density and a ~50% reduction in head width, largely recapitulating the effects of IDOL deficiency.

“ApoER2 overexpression resulted in a 2-fold increase in spine density and a ~50% reduction in head width, largely recapitulating the effects of IDOL deficiency (Figure 4B).”

May combine two claims.

Deletion of IDOL from hippocampal neurons does not change total or surface levels of the GluR1 and GluR2 subunits of the AMPA receptor, nor the NR1, NR2a or NR2b subunits of NMDARs.

“Deletion of IDOL from hippocampal neurons did not change total or surface levels of the GluR1 and GluR2 subunits of the AMPA (α-amino-3-hydrozy-5-methylisoxa-zole-4-propionic acid) receptor, nor the NR1, NR2a or NR2b subunits of NMDARs (Figure 5A).”

May combine two claims.

IDOL-deficient mice show diminished spatial and associative learning.

“IDOL-deficient mice show profound impairment in experience-dependent reorganization of synaptic circuits in the barrel cortex, as well as diminished spatial and associative learning.”

May combine two claims.

IDOL is widely expressed in neurons and is particularly abundant in the CA1 region of the hippocampus.

“β-galactosidase staining of sagittal brain sections from IDOL-deficient mice revealed that IDOL was widely expressed in neurons and was particularly abundant in the CA1 region of the hippocampus (Figure 1A; Figure 1—figure supplement 1A and B).”

May combine two claims.

WT mice spent significantly more time in the target quadrant after 7 or 9 days training, while IDOL-deficient mice showed no improvement.

“WT mice spent significantly more time in the target quadrant after 7 or 9 days training, while IDOL-deficient mice showed no improvement (Figure 8B).”

May combine two claims.

WT mice performed better than IDOL-deficient mice in the Morris water maze with a hidden platform, as measured by reduced escape latencies over training trials, although both groups improved.

“WT mice performed better than IDOL-deficient mice in this task, as measured by reduced escape latencies over the course of the training trials, although both groups improved (Figure 8A).”

May combine two claims.

Bic incubation suppresses Mylip mRNA level after 2 hr, and this is associated with an increase in ApoER2 protein, but no change in its mRNA.

“Bic incubation suppressed Mylip mRNA level after 2 hr, and this was associated with an increase in ApoER2 protein, but no change in its mRNA (Figure 1I,J).”

• AssumptionRests on an assumption: Bicuculline drives glutamatergic activity.

May combine two claims.

Both groups performed similarly in the visible platform test and exhibited comparable swimming speed.

“These performance differences could not be attributed to vision or locomotor defects, as both groups performed similarly in the visible platform test (Figure 8C), and exhibited comparable swimming speed (Figure 8D).”

May combine two claims.

In IDOL-deficient neurons, Bic treatment failed to induce and actually reduced Rac1 activity.

“Interestingly, although IDOL-deficient neurons showed increased basal Rac1 activity, Bic failed to induce, and actually reduced, Rac1 activity (Figure 5E).”

May combine two claims.

IDOL expression reduces mEPSC amplitude but has negligible effects on frequency.

“The recordings of miniature excitatory postsynaptic currents (mEPSCs) at DIV 16–18 showed that IDOL expression reduced their amplitude of but had negligible effects on their frequency (Figure 3A)”

Classified as probably not a substantial claim.

Induction of Rac1 activity downstream of glutamate receptors, particularly NMDAR, plays a central role in promoting actin polymerization and enlargement of the spine head.

“The induction of Rac1 activity downstream of glutamate receptors, particularly NMDAR, plays a central role in promoting actin polymerization and enlargement of the spine head (Xie et al., 2007).”

• cites Xie et al., 2007 sourceNot checked — no full text of the source

May combine two claims.

Either too little or too much ApoER2 is detrimental.

“Either too little or too much ApoER2 is detrimental.”

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

ApoE receptors are members of the low-density lipoprotein receptor gene family that play important roles in maintaining the proper function of neurons.

“ApoE receptors are members of the low-density lipoprotein receptor gene family that play important roles in maintaining the proper function of neurons (Herz and Bock, 2002).”

• cites Herz and Bock, 2002 sourceNot checked — no full text of the source

May combine two claims.

Either too little or too much ApoER2 leads to dysmorphic effects.

“Either too little or too much ApoER2 leads to dysmorphic effects.”

May combine two claims.

The inhibitory effects of IDOL on spinogenesis are largely independent of the Reelin signaling pathway and the uptake of lipoprotein particles in our experimental setting.

“and largely independent of the Reelin signaling pathway and the uptake of lipoprotein particles in our experimental setting.”

• AssumptionRests on an assumption: RAP is a high-affinity competitive ligand for ApoE receptors.
• AssumptionRests on an assumption: CR50 is a neutralizing antibody to Reelin.

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

There is a direct relationship between spine morphology and synaptic function.

“there is a direct relationship between spine morphology and synaptic function (Dillon and Goda, 2005)”

• cites Dillon and Goda, 2005 sourceNot checked — no full text of the source

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

ApoER2 is concentrated in the P2 cellular fraction, which includes postsynaptic densities.

“ApoER2 has been reported to be concentrated in the P2 cellular fraction, which includes postsynaptic densities (Beffert et al., 2005).”

• cites Beffert et al., 2005 sourceNot checked — no full text of the source

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

ApoER2 and VLDLR bind Reelin in addition to ApoE.

“ApoE Receptor 2 (ApoER2/LRP8) and the very low-density lipoprotein receptor (VLDLR) bind Reelin in addition to ApoE”

• cites Herz and Chen, 2006 sourceNot checked — no full text of the source

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

LTD is associated with the shrinkage and elimination of spines.

“whereas LTD is associated with the shrinkage and elimination of spines (Okamoto et al., 2004)”

• cites Okamoto et al., 2004 sourceNot checked — no full text of the source

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

The IDOL-ApoER2 axis modulates the coupling between glutamate receptors and Rac1.

“The IDOL-ApoER2 axis modulates the coupling between glutamate receptors and Rac1”

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

Spines with large heads express higher levels of AMPA receptors and establish stronger synaptic connections.

“Spines with large heads express higher levels of AMPA receptors and establish stronger synaptic connections (Tada and Sheng, 2006).”

• cites Tada and Sheng, 2006 sourceNot checked — no full text of the source

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

Learning and memory are associated with long-term structural changes at synapses.

“Learning and memory are associated with long-term structural changes at synapses (Lamprecht and LeDoux, 2004)”

• cites Lamprecht and LeDoux, 2004 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

JIP1/2 interact with ApoER2.

“It has previously been reported that c-jun-terminal kinase interacting proteins 1/2 (JIP1/2) interact with ApoER2 (Stockinger et al., 2000) as well as Tiam1 (Buchsbaum et al., 2002), the major Rac guanine nucleotide exchange factor that couples the NMDAR to Rac1 (Tolias et al., 2005).”

• cites Stockinger et al., 2000 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

Brief stimulation of postsynaptic NMDAR induces rapid insertion and clustering of AMPA receptors at synapses and consequently enhanced mEPSCs.

“Brief stimulation of postsynaptic NMDAR induces rapid insertion and clustering of AMPA receptors at synapses and consequently enhanced mEPSCs (Lu et al., 2001).”

• cites Lu et al., 2001Not matched

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

May combine two claims.

Excess IDOL activity affects spine formation but not maintenance.

“suggesting that excess IDOL activity affects spine formation but not maintenance.”

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

Spine morphogenesis and remodeling provide a physical basis for memory in neural networks.

“Thus, spine morphogenesis and remodeling provide a physical basis for memory in neural networks (Kasai et al., 2003).”

• cites Kasai et al., 2003 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

JIP1/2 interact with Tiam1.

“It has previously been reported that c-jun-terminal kinase interacting proteins 1/2 (JIP1/2) interact with ApoER2 (Stockinger et al., 2000) as well as Tiam1 (Buchsbaum et al., 2002), the major Rac guanine nucleotide exchange factor that couples the NMDAR to Rac1 (Tolias et al., 2005).”

• cites Buchsbaum et al., 2002 sourceNot checked — no full text of the source

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

Rho family small GTPases are critical molecular switches controlling actin remodeling during spinogenesis.

“Rho family small GTPases are critical molecular switches controlling actin remodeling during spinogenesis (Dillon and Goda, 2005).”

• cites Dillon and Goda, 2005 sourceNot checked — no full text of the source

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

LTP-inducing stimuli cause the formation of new spines and the enlargement of existing ones.

“LTP-inducing stimuli cause the formation of new spines and the enlargement of existing ones (Matsuzaki et al., 2004; Nägerl et al., 2004)”

• cites Matsuzaki et al., 2004 sourceNot checked — no full text of the source
• cites Nägerl et al., 2004 sourceNot checked — no full text of the source

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

ApoER2/VLDLR-mediated Reelin signaling is essential for controlling neuronal migration and positioning during early brain development.

“ApoER2/VLDLR-mediated Reelin signaling is essential for controlling neuronal migration and positioning during early brain development (Herz and Chen, 2006).”

• cites Herz and Chen, 2006 sourceNot checked — no full text of the source

May combine two claims.

Loss of IDOL does not globally disrupt CNS development or basal synaptic transmission.

“Loss of IDOL does not globally disrupt CNS development or basal synaptic transmission, but greatly impairs the functional plasticity of synapses and neural circuits in vivo.”

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

In whole-cell patch recordings, recordings were considered for analysis if at least 50 mEPSCs were collected.

“Recordings were considered for analysis if the series resistance was less than 15 MΩ and if at least 50 mEPSCs were collected.”

May combine two claims.

IDOL-deficient mice show impaired cognitive function and a complete failure to reorganize neural circuits.

“IDOL-deficient neurons are defective in their ability to undergo activity-dependent spine remodeling and IDOL-deficient mice show impaired cognitive function and a complete failure to reorganize neural circuits.”

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

In whole-cell patch recordings, recordings were considered for analysis if the series resistance was less than 15 MΩ.

“Recordings were considered for analysis if the series resistance was less than 15 MΩ and if at least 50 mEPSCs were collected.”

May combine two claims.

ApoER2 lacking the OLS domain is likely still regulated by IDOL in response to neuronal activity, although its dynamics will be based on the higher ApoER2 level.

“ApoER2 lacking the OLS domain is likely still regulated by IDOL in response to neuronal activity, although its dynamics will be based on the higher ApoER2 level.”

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

In in vitro electrophysiology, each slice was subjected to only one particular test, even when different slices from the same animal were used for several experiments.

“Different slices from the same animal were sometimes used for several experiments, including LTP, LTD or paired-pulse facilitation, but each slice was subjected to only one particular test.”

May combine two claims.

Loss of IDOL impairs the coupling between glutamate receptor activation and Rac1, increasing basal Rac1 activity and blocking the activation of Rac1 by neuronal activity.

“Loss of IDOL impairs the coupling between glutamate receptor activation and Rac1, increasing basal Rac1 activity and blocking the activation of Rac1 by neuronal activity.”

May combine two claims.

Knocking down ApoER2 expression reversed the effects of IDOL expression, strongly suggesting that these effects are specific.

“However, our demonstration that knocking down ApoER2 expression reversed the effects of IDOL expression strongly suggests that these effects are specific.”

May combine two claims.

Constitutive ApoER2 expression caused by IDOL deficiency is detrimental to proper dendritic spine morphogenesis and the plasticity of neural circuits.

“On the contrary, we have shown here that the constitutive ApoER2 expression caused by IDOL deficiency is detrimental to proper dendritic spine morphogenesis and the plasticity of neural circuits.”

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

Spatial and temporal coordination of actin dynamics are prerequisite for synapse formation and plasticity.

“Considerable evidence suggests that spatial and temporal coordination of actin dynamics are prerequisite for synapse formation and plasticity (Dillon and Goda, 2005).”

• cites Dillon and Goda, 2005 sourceNot checked — no full text of the source

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

In the Morris water maze test, the experimenter was blind to the genotype of the animals.

“The experimenter was blind to the genotype of the animals.”

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

JIP was originally identified as a putative scaffold that binds components of the JNK signaling pathway.

“The JNK-interacting protein (JIP) was originally identified as a putative scaffold that binds components of the JNK signaling pathway (Whitmarsh et al., 1998).”

• cites Whitmarsh et al., 1998 sourceNot checked — no full text of the source

May combine two claims.

Loss of IDOL completely abolished activity-dependent regulation of ApoER2 levels, which consequently led to impaired structural and functional plasticity of dendritic spines.

“On the contrary, loss of IDOL completely abolished activity-dependent regulation of ApoER2 levels, which consequently led to impaired structural and functional plasticity of dendritic spines.”

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

For each neuron recorded in whole-cell patch recordings, transduction was confirmed by acquiring DIC and fluorescent images after the recording.

“To confirm transduction for each neuron recorded, DIC and florescent images were acquired, following each recording, using a Zeiss Axiovert 200 equipped with a Zeiss Axiocam MR camera and Axiovision acquisition software.”

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

Rho small GTPases (particularly RhoA, Rac1, Cdc42) are regulators of the actin cytoskeleton that have a profound influence on spine morphogenesis.

“The Rho small GTPases (particularly RhoA, Rac1, Cdc42) are regulators of the actin cytoskeleton that have a profound influence on spine morphogenesis (Luo, 2002; Newey et al., 2005).”

• cites Luo, 2002 sourceNot checked — no full text of the source
• cites Newey et al., 2005 sourceNot checked — no full text of the source