BDNF-Dependent Recycling Facilitates TrkB Translocation to Postsynaptic Density during LTP via a Rab11-Dependent Pathway

It may state two separate claims as one.

Monensin attenuates, whereas glycine pretreatment enhances, BDNF-induced TrkB-FL translocation into spines.

“Moreover, treatment of neurons with the endocytic recycling inhibitor monensin (10 M),could attenuate, whereas glycine pretreatment could enhance, the BDNF-induced TrkB-FL translocation into the spines (Fig. 7C), which supports the hypothesis that postendocytic recycled TrkB-FL receptors could translocate into spines.”

It may state two separate claims as one.

BDNF treatment for 1 h significantly decreases the percentage of spines containing TrkB-FL at the base and increases the percentage of spines (~41%) containing TrkB-FL in the head.

“Compared with the baseline, BDNF treatment for 1 h significantly decreased the percentage of spines containing TrkB-FL at the base and accordingly increased the percentage of the spines (ϳ41%) containing TrkB-FL in the head (Fig. 7C), which suggests that BDNF-triggered TrkB-FL endocytosis might facilitate its translocation into spines.”

It may state two separate claims as one.

Rab4S22N significantly inhibits recycling of TrkB.T1, whereas Rab4Q67L enhances TrkB.T1 recycling.

“Conversely, the GDP-locked form of Rab4 (Rab4S22N) could significantly inhibit the recycling of TrkB.T1, whereas the GTP-locked form of Rab4 (Rab4Q67L) enhanced TrkB.T1 recycling (Fig. 5C,D).”

It may state two separate claims as one.

GDP-bound Rab11 weakens, whereas GTP-bound Rab11 enhances, the association between TrkB-FL and PSD-95.

“CO-IP results revealed that GDP-bound Rab11 weakened, whereas GTP-bound Rab11 enhanced, the association between TrkB-FL and PSD-95 (Fig. 8B).”

It may state two separate claims as one.

Most internalized TrkB-FL receptors colocalize with Rab11 but not Rab4 containing vesicles, whereas internalized TrkB.T1 receptors mainly colocalize with Rab4.

“We found that most of the internalized TrkB-FL receptors were colocalized with Rab11 but not Rab4 containing vesicles, whereas internalized TrkB.T1 receptors were mainly colocalized with Rab4 (Fig. 4 D, E).”

It may state two separate claims as one.

Recycled TrkB-FL colocalizes with PSD-95 puncta, and the percentage of colocalization is significantly increased by glycine treatment.

“Using our live-cell antibody feeding assay, we demonstrated the colocalization of recycled TrkB-FL with PSD-95 puncta and found that the percentage of their colocalization was significantly increased by glycine treatment (Fig. 7 D, E).”

It may state two separate claims as one.

In HEK293 cells cotransfected with Myc-Rab11 or Myc-Rab4 and FLAG-TrkB-FL, TrkB-FL associates with Rab11 but not Rab4.

“Interestingly, after immunoprecipitation of Rab proteins with Myc antibodies, an association of TrkB-FL with Rab11 but not Rab4 was observed, as assessed by immunoblotting analysis using FLAG antibodies (Fig. 4A).”

It may state two separate claims as one.

Under basal conditions, TrkB-FL receptors are predominantly localized in the dendritic shaft at the base of spines, and only ~26% of spines contain TrkB-FL in the head.

“Quantitative analyses revealed that, under basal conditions, TrkB-FL receptors were predominantly localized in the dendritic shaft at the base of spines and only ϳ26% of the spines contained TrkB-FL in the head.”

It may state two separate claims as one.

In HEK293 cells overexpressing Rab11 with TrkB-FL, TrkB.T1, or TrkB.KD, only TrkB-FL is pulled down by Rab11; no association between TrkB.T1 or TrkB.KD and Rab11 is detected.

“In HEK293 cells with Rab11 and TrkB-FL, TrkB.T1, or TrkB.KD ectopic overexpression, only TrkB-FL can be pulled down by Rab11, whereas no association between TrkB.T1/Trk-B.KD and Rab11 was detected (Fig. 4B), which suggests that the kinase activity is required for the TrkB-FL/Rab11 interaction.”

It may state two separate claims as one.

cLTP-enhanced TrkB-FL recycling is blocked at endogenous levels by Rab11, but not Rab4, knockdown.

“Moreover, cLTPenhanced TrkB-FL recycling was also blocked at the endogenous levels by Rab11, but not Rab4, knock-down (Fig. 5 E, F ).”

It may state two separate claims as one.

Recycled TrkB.T1 colocalizes with PSD-95, but their colocalization is not further increased by glycine treatment.

“Compared with TrkB-FL, the recycled TrkB.T1 also colocalized with PSD-95, however, their colocalization was not further increased by glycine treatment (Fig. 7 D, E).”

It may state two separate claims as one.

Rab11S25N significantly decreases the colocalization percentage of recycled TrkB-FL with PSD-95 and abolishes the glycine-stimuli-induced increase in their colocalization.

“Introducing in neurons the dominant-negative mutant of Rab11 (Rab11S25N) significantly decreased the colocalization percentage of recycled TrkB-FL with PSD-95 and abolished the glycinestimuli-induced increase in their colocalization (Fig. 7 D, E).”

It may state two separate claims as one.

Knocking down Rab11 by siRNA decreases endogenous recycling of TrkB-FL but not TrkB.T1, whereas Rab4 knockdown abolishes TrkB.T1 recycling at endogenous levels.

“We found that knocking down Rab11 by siRNA decreased the endogenous recycling of TrkB-FL, but not TrkB.T1, whereas Rab4 knock-down abolished TrkB.T1 recycling at the endogenous levels.”

It may state two separate claims as one.

Rab11Q70L significantly increases the association between TrkB-FL and PSD-95, whereas Rab11S25N decreases this association.

“We found that Rab11Q70L significantly increased the association between TrkB-FL and PSD-95, whereas Rab11S25N decreased this association (Fig. 8A).”

It may state two separate claims as one.

Overexpression of Rab11S25N significantly decreases recycling of TrkB-FL receptor, whereas Rab11Q70L increases it.

“Overexpression of Rab11S25N, which is deficient in GTP binding and functions as a dominant-negative mutant of Rab11 (Ascan ˜o et al., 2009), significantly decreased, whereas the constitutively active form of Rab11 (Rab11Q70L) increased the recycling of TrkB-FL receptor (Fig. 5 A, B).”

It may state two separate claims as one.

Endogenous Rab11/TrkB-FL interaction is significantly enhanced by BDNF treatment and abolished by the Trk kinase inhibitor K252a.

“The endogenous Rab11/TrkB-FL interaction was significantly enhanced by BDNF treatment and abolished in the presence of the specific Trk kinase inhibitor K252a (Fig. 4C), which further confirms that their interaction relies on TrkB ki-nase activity.”

It may state two separate claims as one.

siRNA knockdown of Rab11 or Rab4 blocks recycling of TrkB-FL or TrkB.T1, respectively.

“To further confirm the role of Rab11 and Rab4 in mediating recycling of the two TrkB receptors, we demonstrated that siRNA knocking down Rab11 or Rab4 expression could, respectively, block the recycling of TrkB-FL or TrkB.T1 (Fig. 5A-D).”

It may state two separate claims as one.

Rab11 interacts and colocalizes with TrkB-FL.

“Figure 4. Rab11 interacts and colocalizes with TrkB-FL.”

Probably not a substantial claim. The paper may give no reason why it holds.

cLTP stimuli promote the switch of Rab11 to its active form.

“cLTP stimuli could promote the switch of Rab11 to its active form and thus facilitate TrkB-FL binding with PSD-95, which could in part explain the cLTP-induced translocation of recycled TrkB-FL into PSD.”

It may state two separate claims as one.

cLTP stimulation blocks BDNF-induced TrkB-FL degradation, an effect abolished by coapplication of the NMDA receptor antagonist D-AP5.

“We found that cLTP stimulation could block BDNF-induced TrkB-FL degradation, an effect that was abolished by coapplication of the NMDA receptor antagonist D-AP5.”

It may state two separate claims as one.

TrkB-FL and TrkB.T1 receptors are sorted into the Rab11- or Rab4-dependent recycling pathway, respectively.

“Figure 5. TrkB-FL and TrkB.T1 receptors are sorted into the Rab11-or Rab4-dependent recycling pathway, respectively.”

It may state two separate claims as one.

Increased TrkB-FL recycling upon cLTP stimuli enhances BDNF-induced sustained but not transient ERK and PI3K-AKT activation.

“Figure 6.Increased TrkB-FL recycling upon cLTP stimuli enhances BDNF-induced sustained but not transient ERK and PI3K-AKT activation.”

It may state two separate claims as one.

cLTP stimuli enhance the postendocytic recycling of TrkB-FL receptors, but not TrkB.T1 receptors.

“Figure 2. cLTP stimuli enhance the postendocytic recycling of TrkB-FL receptors, but not TrkB.T1 receptors.”

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

BDNF elicits rapid effects on synaptic transmission and membrane excitability primarily via activation of these signaling pathways downstream of TrkB.

“BDNF elicits rapid effects on synaptic transmission and membrane excitability primarily via activation of these signaling pathways downstream of its TrkB receptor (Poo, 2001;Rose et al., 2004).”

• cites Poo, 2001 sourceNot checked — no full text of the source
• cites Rose et al., 2004 sourceNot checked — no full text of the source

It may state two separate claims as one.

Transient activation of TrkB and downstream signaling are independent of recycling and degradation.

“which suggested that the transient activation of TrkB and its down-stream signaling were independent of recycling and degradation.”

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

BDNF is involved in mediating higher-order activities such as learning, memory, and behavior.

“Due to its essential role in synaptic plasticity modulation, BDNF is also involved in mediating higher-order activities such as learning, memory, and behavior (Yu et al., 2009;Cunha et al., 2010).”

• cites Yu et al., 2009Not matched

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

• cites Cunha et al., 2010Not matched

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

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

Stimuli that trigger LTP promote recycling of AMPA receptor-containing endosomes for modifying synaptic strength, regulated by Rab GTPases, Myosin V, and GRIP-associated protein-1.

“Recent studies have demonstrated that stimuli that triggered LTP promote recycling of the AMPA receptors containing endosomes for modifying synaptic strength, a process that was regulated by Rab GTPases, molecular motor Myosin V, and adaptor protein GRIP-associated protein-1 (Park et al., 2004;Correia et al., 2008;Wang et al., 2008;Hoogenraad et al., 2010).”

• cites Park et al., 2004 sourceNot checked — no full text of the source
• cites Correia et al., 2008Not matched

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

• cites Wang et al., 2008 sourceNot checked yet

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

Ultrastructural analysis indicates a large variety of recycling compartments and vesicles serve multiple dendritic spines, most with recycling endosomes at their base.

“Ultrastructural analysis has indicated a large variety of recycling compartments and vesicles that serve multiple dendritic spines, most of which had recycling endosomes at their base (Cooney et al., 2002;Park et al., 2006).”

• cites Cooney et al., 2002 sourceNot checked yet
• cites Park et al., 2006 sourceNot checked — no full text of the source

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

cLTP induces rapid TrkB insertion into the postsynaptic membrane, which requires Cdk5 activity.

“Our recent work also has demonstrated that chemical LTP (cLTP) could induce rapid TrkB insertion into the postsynaptic membrane, which requires the activity of cyclindependent kinase 5 (Zhao et al., 2009).”

• cites Zhao et al., 2009 sourceNot checked — no full text of the source

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

TrkB activation by BDNF initiates three major signaling cascades: phospholipase Cγ, PI3K, and ERK.

“TrkB activation by BDNF initiates three major cascades of signaling pathways: phospholipase C␥, phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated kinase (ERK) (Huang and Reichardt, 2003;Segal, 2003).”

• cites Huang and Reichardt, 2003 sourceNot checked — no full text of the source
• cites Segal, 2003 sourceNot checked — no full text of the source

It may state two separate claims as one.

TrkB-FL and TrkB.T1 receptors are sorted into distinct recycling pathways via Rab11 and Rab4, respectively.

“TrkB-FL and TrkB.T1 receptors are sorted into distinct recycling pathways via Rab11 and Rab4, respectively”

It may state two separate claims as one.

Rab11 and Rab4 are required for the postendocytic recycling of TrkB-FL and TrkB.T1 receptors, respectively.

“These results demonstrate that Rab11 and Rab4 are required for the postendocytic recycling of TrkB-FL and TrkB.T1 receptors, respectively.”

It may state two separate claims as one.

Rab11 and Rab4, respectively, mediate TrkB-FL and TrkB.T1 receptor postendocytic recycling and thus modulate their surface levels after BDNF treatment.

“These results suggest that Rab11 and Rab4, respectively, mediate TrkB-FL and TrkB.T1 receptor postendocytic recycling and thus modulate their surface levels after BDNF treatment.”

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

BDNF can efficiently drive TrkB receptor internalization, and endocytosed TrkB receptors can either traffic to lysosomes for degradation or recycle back to the plasma membrane.

“BDNF can efficiently drive TrkB receptor internalization and endocytosed TrkB receptors could either traffic to lysosomes for degradation or recycle back to the plasma membrane (Chen et al., 2005;Huang et al., 2009).”

• cites Chen et al., 2005 sourceCheck pending
• cites Huang et al., 2009 sourceCheck pending

It may state two separate claims as one.

Glycine stimulation activates NMDA receptors and is used to induce cLTP in cultured hippocampal neurons.

“We used a cell culture model using glycine stimulation to activate NMDA receptors, which is used to induce cLTP in cultured hippocampal neurons (Lu et al., 2001; Fig. 1A).”

• cites Lu et al., 2001Not matched

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

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

Neuronal activity increases cell surface TrkB receptor levels, facilitating enhanced responsiveness of active neurons to BDNF.

“Interestingly, neuronal activity has been shown to increase cell surface TrkB receptors levels, thus facilitating the enhanced responsiveness of active neurons to BDNF (Meyer-Franke et al., 1998;Du et al., 2000).”

• cites Meyer-Franke et al., 1998 sourceNot checked — no full text of the source
• cites Du et al., 2000Not matched

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

It may state two separate claims as one.

Neuronal activity significantly increases BDNF-dependent postendocytic recycling of TrkB-FL receptors, but not TrkB.T1 receptors.

“These results suggest that neuronal activity could significantly increase the BDNF-dependent postendocytic recycling of TrkB-FL receptors, but not TrkB.T1 receptors, explaining the blockade effect of cLTP stimuli on BDNF-induced TrkB-FL degradation.”

• Also stated in: § Abstract · boosted

  “We show in cultured rat hippocampal neurons that chemical LTP (cLTP) stimuli selectively promote endocytic recycling of BDNF-dependent full-length TrkB (TrkB-FL) receptors, but not isoform T1 (TrkB.T1) receptors, via a Rab11-dependent pathway.”

It may state two separate claims as one.

LTP is attenuated in slices pretreated with TrkB-IgG or from BDNF knock-out mice.

“Conversely, LTP was attenuated in slices pretreated with the fusion protein TrkB-IgG or in slices obtained from BDNF knock-out mice (Korte et al., 1995;Patterson et al., 1996).”

• cites Korte et al., 1995 sourceNot checked — no full text of the source
• cites Patterson et al., 1996 sourceNot checked yet

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

Glycine-induced cLTP increases the number of functional AMPA-type glutamate receptors at the postsynaptic membrane, leading to increased AMPAR-mediated transmission at excitatory synapses, as in other LTP models.

“Glycine-induced cLTP could increase the number of functional AMPA-type glutamate receptors at the postsynaptic membrane, leading to an increase in AMPAR-mediated transmission at excitatory synapses, as in other LTP models (Isaac et al., 1995;Liao et al., 1995;Lu et al., 2001;Park et al., 2004).”

• cites Isaac et al., 1995 sourceNot checked — no full text of the source
• cites Liao et al., 1995 sourceNot checked — no full text of the source
• cites Lu et al., 2001Not matched

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

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

Internalized receptors recycle to the plasma membrane via two distinct pathways: Rab4 regulates fast recycling from early endosomes to the cell surface, and Rab11 mediates slow recycling from perinuclear recycling vesicles to the plasma membrane.

“Upon delivery to the early endosomes, internalized receptors then recycle to the plasma membrane via two distinct recycling pathways: Rab4 regulates fast recycling from early endosomes to the cell surface (Sheff et al., 1999), whereas Rab11 plays a role in slow recycling from perinuclear recycling vesicles back to the plasma membrane.”

• cites Sheff et al., 1999 sourceNot checked yet

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

Internalized β2-adrenergic receptors efficiently recycle back to the plasma membrane via direct interaction with Rab11.

“It has been previously reported that internalized ␤(2)-adrenergic receptors efficiently recycled back to the plasma membrane via direct interaction with Rab11 (Parent et al., 2009).”

• cites Parent et al., 2009Not matched

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

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

Inactive Rab protein is in a soluble cytosolic form and activated Rabs are membrane bound.

“It has been reported that the inactive Rab protein is in a soluble cytosolic form and the activated Rabs were membrane bound (Grosshans et al. , 2006).”

• cites Grosshans et al., 2006 sourceNot checked — no full text of the source

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

BDNF, released in an activity-dependent manner, binds and activates TrkB receptors.

“BDNF, released in an activity-dependent manner, binds and activates tropomyosin related kinase B (TrkB) receptors (Greenberg et al., 2009).”

• cites Greenberg et al., 2009 sourceNot checked yet

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

Both TrkB-FL and TrkB.T1 receptors are expressed in neurons because of alternative splicing; TrkB.T1 lacks the kinase domain but contains a short isoform-specific cytoplasmic domain.

“Both full-length TrkB (TrkB-FL) and its isoform T1 (TrkB.T1) receptors, which lack the kinase domain but contain short isoform-specific cytoplasmic domain in its place, are expressed in neurons because of alternative splicing (Klein et al., 1990).”

• cites Klein et al., 1990 sourceNot checked — no full text of the source

Probably not a substantial claim.

TrkB is found in the postsynaptic density (PSD).

“Previous studies had indicated that TrkB was found in the postsynaptic density (PSD) (Ji et al., 2005).”

• cites Ji et al., 2005Not matched

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

It may state two separate claims as one.

Internalized TrkB-FL and TrkB.T1 receptors may traverse the Rab11- or Rab4-dependent recycling pathway, respectively.

“These results suggest that the internalized TrkB-FL and TrkB.T1 receptors may traverse the Rab11-or Rab4-dependent recycling pathway, respectively.”

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

Exogenous BDNF promotes the induction of LTP in young hippocampal slices.

“Exogenous BDNF promotes the induction of long-term potentiation (LTP) in young hippocampal slices (Figurov et al., 1996).”

• cites Figurov et al., 1996 sourceNot checked — no full text of the source

Probably not a substantial claim.

BDNF plays an important role in the activity-dependent regulation of synaptic structure and function via TrkB receptor activation.

“Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function via tropomyosin related kinase B (TrkB) receptor activation.”

• Also stated in: § Introduction · plain

  “Brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function (Arancio and Chao, 2007).”

• cites Arancio and Chao, 2007 sourceNot checked — no full text of the source

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

Sec15 is an effector protein of Rab11 and only binds to GTP-bound Rab11 with its C-terminal domain.

“A GST pull-down assay with Sec15, which has been shown to be an effector protein of Rab11 and only binds to GTP-bound Rab11 with its C-terminal domain (Zhang et al., 2004;Wu et al., 2005), was used to test the Rab11 activity directly.”

• cites Zhang et al., 2004 sourceCheck pending
• cites Wu et al., 2005Not matched

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

It may state two separate claims as one.

cLTP stimuli facilitate recycled TrkB-FL, but not TrkB.T1, translocation into postsynaptic densities via a Rab11-dependent pathway.

“These data indicate that cLTP stimuli could facilitate recycled TrkB-FL, but not TrkB.T1, translocation into postsynaptic densities via a Rab11-dependent pathway.”

It may state two separate claims as one.

The Rab11-dependent, but not the Rab4-dependent, pathway mediates cLTP-enhanced TrkB-FL recycling.

“which suggested that the Rab11dependent, but not the Rab4-dependent, pathway mediated cLTP-enhanced TrkB-FL recycling.”

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

Delivery of new AMPARs during LTP into synapses requires two distinct steps: Rab11-driven endosomes mediate translocation of AMPARs into spines, and Rab8 mediates final insertion into synaptic membrane.

“Previous studies have found that the delivery of new AMPARs during LTP into synapses requires two distinct steps.First, Rab11-driven endosomes mediate the translocation of AMPARs into spines and then Rab8 mediates the final insertion of AMPARs into the synaptic membrane (Brown et al., 2007).”

• cites Brown et al., 2007 sourceCheck pending

It may state two separate claims as one.

cLTP specifically enhances the recycling of TrkB-FL, but not TrkB.T1, suggesting that LTP might have a specific effect on the Rab11-dependent recycling pathway rather than globally regulate the recycling system.

“However, in our study, we demonstrated that cLTP could specifically enhance the recycling of TrkB-FL, but not TrkB.T1, which suggested that LTP might have a specific effect on Rab11dependent recycling pathway rather than globally regulate the recycling system.”

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

Rab proteins function as molecular switches and, when active, are anchored at the cytoplasmic face of membranous organelles, where they direct membrane trafficking events such as vesicle formation, motility, docking, and fusion.

“Rab proteins function as molecular switches and, when active, are anchored at the cytoplasmic face of membranous organelles, where they direct membrane trafficking events, such as vesicle formation, motility, docking, and fusion (Stenmark, 2009).”

• cites Stenmark, 2009 sourceNot checked — no full text of the source

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

TrkB-FL and TrkB.T1 receptors are both efficiently endocytosed by BDNF treatment.

“It has been established that TrkB-FL and TrkB.T1 receptors are both efficiently endocytosed by BDNF treatment (Huang et al., 2009).”

• cites Huang et al., 2009 sourceCheck pending

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

Synaptic TrkB-FL receptors play an important role in synaptic transmission and LTP.

“Previous studies have indicated that TrkB seems to be distributed throughout the neuron, including the soma, dendrite, and axon (Kryl et al., 1999), and that synaptic TrkB-FL receptors play an important role in synaptic transmission and LTP (Poo, 2001).”

• cites Poo, 2001 sourceNot checked — no full text of the source

Probably not a substantial claim. The authors may not put it forward as true. It may state two separate claims as one.

LTP stimuli promote recycling of AMPARs and transferrin receptors, suggesting that LTP involves a global regulation of the recycling system rather than a specific regulation of AMPAR trafficking through recycling endosomes.

“Interestingly, they found that LTP stimuli promoted recycling not only of AMPARs, but also of transferrin receptors, and suggested that LTP involves a global regulation of the recycling system, rather than a specific regulation of AMPAR trafficking through recycling endosomes.”

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

Probably not a substantial claim.

Activation of PI3K and ERK pathways plays essential roles in LTP induction and maintenance.

“Previous studies have demonstrated that the activation of PI3K and ERK pathways play essential roles in LTP induction and maintenance (Man et al., 2003;Kelleher et al., 2004;Tsokas et al., 2007).”

• cites Man et al., 2003 sourceNot checked — no full text of the source
• cites Kelleher et al., 2004 sourceNot checked — no full text of the source
• cites Tsokas et al., 2007 sourceCheck pending

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

TrkB-FL receptors interact with PSD-95, and this interaction can be regulated by neuronal activity.

“Though TrkB-FL receptors have been shown previously to interact with PSD-95, and this interaction could be regulated by neuronal activity, the underlying molecular mechanism is still unclear (Yoshii and Constantine-Paton, 2007).”

• cites Yoshii and Constantine-Paton, 2007 sourceNot checked — no full text of the source

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

Upon internalization, TrkB receptors are sorted in early endosomes either to a specialized recycling endosome compartment for reinsertion to the plasma membrane or to late endosomes and lysosomes for degradation.

“Upon internalization, TrkB receptors are sorted in early endosomes either to a specialized recycling endosome compartment for reinsertion to the plasma membrane or to late endosomes and lysosomes for degradation (Chen et al., 2005).”

• cites Chen et al., 2005 sourceCheck pending

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

The increased recycling of transferrin receptors during LTP might also be mediated via the Rab11-dependent pathway.

“These studies suggested that the increased recycling of the transferrin receptors during LTP might also be mediated via the Rab11-dependent pathway.”

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

Recycled and resecreted BDNF plays an important role in mediating the maintenance of LTP in hippocampal slices.

“A recent study has shown that recycled and resecreted BDNF plays an important role in mediating the maintenance of LTP in hippocampal slices, which suggests a potential role of TrkB recycling in LTP regulation (Santi et al., 2006).”

• cites Santi et al., 2006 sourceCheck pending

It may state two separate claims as one.

The cLTP-induced translocation of recycled TrkB-FL into PSD can be in part explained by cLTP promoting Rab11 activation and facilitating TrkB-FL binding with PSD-95.

“cLTP stimuli could promote the switch of Rab11 to its active form and thus facilitate TrkB-FL binding with PSD-95, which could in part explain the cLTP-induced translocation of recycled TrkB-FL into PSD.”

• AssumptionRests on an assumption: To elicit synapse-specific modulation, functional TrkB must be localized at synapses and preferably modulated by synaptic activity.

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

TrkB is distributed throughout the neuron, including the soma, dendrite, and axon.

“Previous studies have indicated that TrkB seems to be distributed throughout the neuron, including the soma, dendrite, and axon (Kryl et al., 1999), and that synaptic TrkB-FL receptors play an important role in synaptic transmission and LTP (Poo, 2001).”

• cites Kryl et al., 1999 sourceCheck pending

Probably not a substantial claim.

Expression of dominant-negative Rab11 specifically inhibits transferrin receptor recycling.

“Expression of dominant-negative Rab11 has been shown to specifically inhibit transferrin receptor recycling (Daro et al., 1996;Ren et al., 1998).”

• cites Daro et al., 1996 sourceNot checked — no full text of the source
• cites Ren et al., 1998 sourceCheck pending

It may state two separate claims as one.

Neuronal-activity-dependent recycling of TrkB-FL is involved in the trophic actions of BDNF and explains at least in part the preferential effect of BDNF on active neurons.

“which suggested that neuronal-activity-dependent recycling of TrkB-FL is involved in the trophic actions of BDNF and explained at least in part the preferential effect of BDNF on active neurons.”

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

Neuronal activity enhances endocytosis of the BDNF-TrkB complex.

“It has been shown that neuronal activity could enhance endocytosis of the BDNF-TrkB complex (Du et al., 2003), so the increased TrkB-FL endocytosis and recycling during LTP could act synergistically to supply more functional TrkB receptors to the PSD for synaptic plasticity modulation.”

• cites Du et al., 2003Not matched

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

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

All experiments were repeated a minimum of three times and representative data are shown.

“All experiments were repeated a minimum of three times and representative data are shown.”

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

Rab11 regulates the intracellular trafficking of the TPβ receptor by a direct interaction.

“In a previous study, Rab11 was shown to regulate the intracellular trafficking of the TP␤ receptor by a direct interaction (Hamelin et al., 2005).”

• cites Hamelin et al., 2005 sourceCheck pending

It may state two separate claims as one.

Increased recycling of TrkB-FL, but not its isoform TrkB.T1, during cLTP could increase cell surface TrkB-FL receptor levels and thus facilitate BDNF signaling for synaptic plasticity modulation.

“The increased recycling of TrkB-FL, but not its isoform TrkB.T1, during cLTP could increase the cell surface TrkB-FL receptor levels and thus facilitate BDNF signaling for synaptic plasticity modulation.”

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

BDNF is a survival promoting factor for hippocampal neurons.

“It is well known that BDNF is a survival promoting factor for hippocampal neurons (Chao, 2003).”

• cites Chao, 2003 sourceNot checked — no full text of the source

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

TrkB.T1 can inhibit TrkB-FL tyrosine kinase signaling through a dominant-negative mechanism both in vitro and in vivo.

“A number of studies have suggested that TrkB.T1 can inhibit TrkB-FL tyrosine kinase signaling through a dominant-negative mechanism both in vitro and in vivo (Carim-Todd et al., 2009).”

• cites Carim-Todd et al., 2009 sourceCheck pending

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

Neurons have smaller transferrin/Rab11-positive endosomal-recycling compartments positioned at the base of dendritic spines.

“In addition, neurons also have smaller transferrin/Rab11-positive endosomal-recycling compartment that are positioned at the base of dendritic spines (Ehlers, 2000;Cooney et al., 2002).”

• cites Ehlers, 2000 sourceNot checked — no full text of the source
• cites Cooney et al., 2002 sourceNot checked yet

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

GluA1-containing AMPARs are inserted at the synaptic plasma membrane in response to LTP-inducing stimuli via the Rab11-dependent recycling pathway.

“Park et al. (2004)found GluA1-containing AMPARs inserted at the synap- tic plasma membrane in response to LTP-inducing stimuli via Rab11-dependent recycling pathway.”

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

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

TrkB.T1 is dynamically upregulated during fetal development and becomes the predominant Trk receptor isoform in the adult animal.

“TrkB.T1 is dynamically upregulated during fetal development and becomes the predominant Trk receptor isoform in the adult animal (Escando ´n et al., 1994).”

• cites Escandón et al., 1994 sourceCheck pending

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

Recycling of endocytic TrkB-FL receptors occurs in a sequence-directed regulated recycling pathway that relies on its tyrosine kinase activity and hepatocyte growth factor-regulated tyrosine kinase substrate.

“We have previously found that recycling of endocytic TrkB-FL receptors occurs in a sequence-directed regulated recycling pathway that relies on its tyrosine kinase activity and hepatocyte growth factor-regulated tyrosine kinase substrate (Huang et al., 2009).”

• cites Huang et al., 2009 sourceCheck pending