Affinage

NTRK2

BDNF/NT-3 growth factors receptor · UniProt Q16620

Length
822 aa
Mass
92.0 kDa
Annotated
2026-04-29
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NTRK2 (TrkB) is a receptor tyrosine kinase that transduces BDNF and NT-4/5 signals through PLCγ1, MAPK/ERK, and PI3K/Akt cascades to control synaptic plasticity, neuronal survival, and cell fate decisions across neuronal and non-neuronal cell types. Upon BDNF binding, TrkB autophosphorylates and recruits PLCγ1 via the Y816 docking site to drive CaMKIV/CREB-dependent hippocampal LTP and limbic epileptogenesis, while a parallel Shc-dependent pathway activates MAPKs; autocrine BDNF–TrkB signaling at single dendritic spines, gated by NMDAR/CaMKII-mediated BDNF release and activity-dependent surface TrkB upregulation, is required for both structural and functional LTP (PMID:12367511, PMID:20445044, PMID:27680698, PMID:24634513). Antidepressants and psychedelics directly bind the TrkB transmembrane domain at a cholesterol-sensing site to allosterically promote BDNF signaling and synaptic plasticity, while PTPσ dephosphorylates TrkB and is displaced by fluoxetine to reopen critical-period plasticity (PMID:33606976, PMID:37280397, PMID:33293360). The truncated isoform TrkB.T1, which lacks kinase activity, functions as both a dominant-negative inhibitor of full-length TrkB and an independent signaling molecule that signals through Rho GTPases in astrocytes to regulate glycine transporter internalization, astrocyte morphological maturation, and excitatory synaptogenesis, and can also promote glioma progression via PI3K/Akt/STAT3 (PMID:11162678, PMID:26200505, PMID:31433295, PMID:32532995).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Establishing that TrkB is a signal-transducing receptor for BDNF resolved the question of how neurotrophins activate intracellular cascades: BDNF induces TrkB tyrosine phosphorylation and downstream PLCγ1, ERK1/2, and PI3K activation to promote neuronal survival and neurite outgrowth.

    Evidence BDNF stimulation of neuroblastoma cells with immunoprecipitation/Western blot for phospho-TrkB and downstream effectors, plus functional survival and outgrowth assays

    PMID:8264643

    Open questions at the time
    • Relative contributions of PLCγ1, ERK, and PI3K arms to specific neuronal outcomes not dissected
    • Whether signaling is cell-autonomous vs. paracrine in vivo unresolved
  2. 1999 Medium

    Mapping the dual-promoter (P1/P2) architecture of the trkB gene and showing that both promoters independently generate kinase-containing and truncated isoforms established the transcriptional basis for TrkB isoform diversity.

    Evidence Promoter deletion/reporter assays, RNase protection mapping, and RT-PCR across tissues

    PMID:10395916

    Open questions at the time
    • Regulatory inputs controlling promoter choice in specific cell types not identified
    • Post-transcriptional regulation of isoform ratio not addressed
  3. 2001 Medium

    Demonstrating that truncated TrkB.T1 inhibits full-length TrkB by direct physical interaction rather than by sequestering BDNF revealed that TrkB.T1 functions as a bona fide dominant-negative receptor.

    Evidence Co-immunoprecipitation of TrkB.T1 with TrkB.TK+ in PC12 cells, BDNF-neutralizing antibody controls, and survival assays

    PMID:11162678

    Open questions at the time
    • Stoichiometry and in vivo relevance of TrkB.T1/TrkB.FL heterodimers not determined
    • Whether TrkB.T1 has autonomous signaling capacity was not tested
  4. 2002 High

    Genetic dissection of TrkB docking sites resolved which downstream pathway drives LTP: PLCγ1 recruitment at Y816 is required for hippocampal LTP and CaMKIV/CREB activation, while the Shc site activates MAPKs in a parallel but LTP-dispensable pathway.

    Evidence Knock-in mice with Y816F (PLCγ) or Y515F (Shc) mutations; hippocampal LTP recordings and Western blots for CaMKIV, CREB, MAPK phosphorylation

    PMID:12367511

    Open questions at the time
    • Whether the Shc pathway contributes to other forms of plasticity not tested
    • Downstream targets of PLCγ1 beyond CaMKIV/CREB not mapped
  5. 2004 High

    Discovering that TrkB suppresses anoikis via PI3K/Akt activation expanded TrkB's role beyond neurobiology to cancer, establishing it as a metastasis-enabling oncogene in epithelial cells.

    Evidence Genome-wide anoikis screen; TrkB overexpression in epithelial cells with PI3K inhibitor experiments; mouse tumor and metastasis models

    PMID:15329723

    Open questions at the time
    • Whether endogenous TrkB ligands drive this phenotype in human cancers not determined
    • Kinase vs. scaffold function not yet separated
  6. 2007 High

    Structure-function analysis showing that TrkB kinase activity, not its extracellular adhesion domains, is necessary and sufficient for anoikis suppression and metastasis clarified the mechanistic basis of TrkB oncogenic action.

    Evidence Kinase-dead and extracellular domain mutants tested in anoikis assays and mouse tumor/metastasis models

    PMID:17616679

    Open questions at the time
    • Identity of the activating ligand in the tumor microenvironment remains unknown
    • Whether kinase inhibitors can reverse established metastasis not tested
  7. 2006 Medium

    Identification of the Y722C NTRK2 mutation as impairing BDNF-induced MAPK, PLCγ, and Akt signaling linked a specific NTRK2 variant to impaired neurite outgrowth and cell survival, providing a functional basis for the obesity-associated phenotype.

    Evidence Wild-type vs. Y722C TrkB in PC12 cells; Western blot for phospho-MAPK, -PLCγ, -Akt; neurite outgrowth and survival assays

    PMID:16702999

    Open questions at the time
    • Causality in human obesity not established by family genetics in this study
    • Structural mechanism of Y722C impairment not resolved
  8. 2010 High

    Three contemporaneous studies deepened the mechanistic picture: TrkB-PLCγ1 signaling at Y816 was shown to be required for limbic epileptogenesis; Src family kinases were found to transactivate TrkB independently of its own kinase via Tyr-705/706 phosphorylation; and N-acetylserotonin was identified as a non-neurotrophin TrkB agonist with circadian and antidepressant activity.

    Evidence trkB(PLC/PLC) knock-in mice in epilepsy models; SFK inhibitors and chemical genetics in cultured neurons; TrkB phosphorylation assays in BDNF-KO mice with behavioral tests

    PMID:20064930 PMID:20133677 PMID:20445044

    Open questions at the time
    • NAS-TrkB direct binding site not identified
    • Whether SFK transactivation of TrkB is relevant in vivo not confirmed
    • Relative contribution of PLCγ1 vs. other arms to epileptogenesis not quantified
  9. 2012 Medium

    TrkB was shown to function as a synaptic tag for memory consolidation, and calpain-mediated cleavage of TrkB-FL during excitotoxicity was found to shift the TrkB-FL/T1 balance toward kinase-inactive forms, contributing to neuronal death.

    Evidence Hippocampal slice electrophysiology with TrkB inhibition during synaptic tagging; calpain inhibitors plus lentiviral TrkB-FL/T1 rebalancing in excitotoxicity models

    PMID:21849537 PMID:22258407

    Open questions at the time
    • Identity of the plasticity-related proteins captured by TrkB tag unknown
    • Whether calpain cleavage product is functionally equivalent to TrkB.T1 not confirmed
  10. 2014 Medium

    Two discoveries extended TrkB signaling regulation: CaMKII-dependent surface TrkB upregulation converts transient BDNF signaling to sustained mode for dendritic branching, and oocyte-specific Ntrk2 deletion causes infertility by ablating gonadotropin-induced PI3K/Akt survival signaling.

    Evidence KCl/theta-burst stimulation of cultured neurons with surface TrkB quantification and CaMKII inhibition; oocyte-specific Ntrk2 conditional KO mice with PI3K/Akt readouts

    PMID:24634513 PMID:24877631

    Open questions at the time
    • Molecular mechanism of CaMKII-driven TrkB surface insertion not identified
    • How kisspeptin and BDNF signals converge on NTRK2.FL transcription not resolved
  11. 2015 High

    Slitrk5 was identified as a TrkB-interacting protein that directs BDNF-dependent TrkB recycling to Rab11-positive endosomes via Rab11-FIP3, and truncated TrkB.T1 in astrocytes was shown to signal through Rho GTPases to internalize glycine transporters, establishing TrkB.T1 as an independent signaling receptor.

    Evidence Co-IP and SIM for Slitrk5–TrkB; Slitrk5 KO mice; radiolabeled glycine uptake with Rho inhibitors and TrkB.T1 shRNA in astrocytes

    PMID:26004511 PMID:26200505

    Open questions at the time
    • Whether Slitrk5-dependent recycling affects specific TrkB signaling outputs not tested
    • Direct TrkB.T1 effector downstream of Rho GTPases not identified
  12. 2016 High

    Single-spine imaging demonstrated that autocrine BDNF release from stimulated spines activates TrkB on those same spines in an NMDAR- and CaMKII-dependent manner, establishing TrkB as a spatially restricted mediator of input-specific structural and functional LTP.

    Evidence FRET-based TrkB sensor with two-photon FLIM; pHluorin-BDNF release imaging; EM localization; pharmacological dissection in hippocampal slice culture

    PMID:27680698

    Open questions at the time
    • How spatial restriction of autocrine signaling is maintained against lateral diffusion unknown
    • Contribution of heterosynaptic TrkB signaling not assessed
  13. 2019 High

    Astrocyte-specific TrkB.T1 deletion revealed that TrkB.T1 is required for astrocyte morphological maturation and normal excitatory synaptogenesis, establishing a non-neuronal cell-autonomous role for this kinase-dead isoform.

    Evidence Global and astrocyte-specific TrkB.T1 conditional KO mice; astrocyte morphology, RNA-seq, and synaptogenesis co-culture assays

    PMID:31433295

    Open questions at the time
    • Downstream signaling pathway from TrkB.T1 to astrocyte morphology not fully delineated
    • Whether TrkB.T1 loss in astrocytes contributes to disease phenotypes not tested
  14. 2020 High

    Two discoveries addressed TrkB regulation and non-neuronal roles: PTPσ was identified as a phosphatase that physically interacts with TrkB to restrain its phosphorylation (disrupted by fluoxetine to reopen critical-period plasticity), and TrkB.T1 was shown to enhance PDGF-driven glioma via ligand-independent PI3K/Akt/STAT3 signaling.

    Evidence Co-IP of TrkB–PTPσ; PTPσ-KO mice; ocular dominance plasticity assays; PDGF-driven glioma model with TrkB.T1 signaling analysis

    PMID:32532995 PMID:33293360

    Open questions at the time
    • Structural basis of fluoxetine-mediated disruption of TrkB–PTPσ interaction not resolved
    • Whether TrkB.T1 directly binds PDGFR or acts indirectly not determined
  15. 2021 High

    Antidepressants were shown to directly bind the TrkB transmembrane domain at a cholesterol-sensing site, and ketamine's rapid synaptic potentiation was found to require postsynaptic TrkB in CA1 neurons via a dynamin1-dependent mechanism, establishing TrkB as a direct pharmacological target of antidepressants.

    Evidence MD simulations; radiolabeled binding; TrkB TM mutagenesis; behavioral tests; region-specific Cre-mediated TrkB deletion with slice electrophysiology

    PMID:33606976 PMID:34407417

    Open questions at the time
    • High-resolution structure of antidepressant–TrkB TM complex not yet available
    • Mechanism linking dynamin1 to TrkB activation by ketamine not fully elucidated
  16. 2022 Medium

    The finding that senescent cells upregulate TrkB and use autocrine BDNF–TrkB–ERK5–BCL2L2 signaling for survival, with TrkB inhibition acting as a senolytic, extended TrkB function to cellular senescence and aging biology.

    Evidence Drug library screen; TrkB KO and BDNF knockdown in senescent cells; apoptosis assays; TrkB inhibitor treatment of aged mice

    PMID:36266274

    Open questions at the time
    • Which TrkB isoform mediates senescent cell survival not specified
    • Whether TrkB senolytic effects translate to human aging not tested
  17. 2023 High

    Psychedelics were found to bind TrkB's transmembrane domain at a site overlapping with but distinct from that of conventional antidepressants, with ~1000-fold higher affinity, and their plasticity and antidepressant effects are TrkB-dependent and 5-HT2A-independent, reframing the mechanism of psychedelic action.

    Evidence Radioligand binding; MD simulations; TrkB mutagenesis; 5-HT2A KO mice; behavioral and plasticity measurements

    PMID:37280397

    Open questions at the time
    • Atomic-resolution co-structure of psychedelic bound to TrkB TM domain not solved
    • Whether all psychedelic therapeutic effects are TrkB-mediated not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the TrkB transmembrane dimer with bound antidepressants/psychedelics is needed to explain allosteric coupling to the extracellular and kinase domains, and the in vivo logic by which TrkB.T1 signals through Rho GTPases in astrocytes remains mechanistically incomplete.
  • No crystal or cryo-EM structure of TrkB transmembrane domain with drug ligands
  • Direct Rho GTPase effector downstream of TrkB.T1 not identified
  • How cholesterol and antidepressant binding cooperate at the TM site is structurally unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3
Partners
BDNFDOK5EFNA5PLCG1PTPRSSHC1SLITRK5

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TrkB mediates hippocampal long-term potentiation via recruitment of PLCγ at the Y816 docking site, with subsequent phosphorylation of CaMKIV and CREB; the Shc docking site is not required for LTP but activates MAPKs in a parallel pathway Targeted knock-in mice with mutations in TrkB Shc or PLCγ docking sites (trkB(SHC/SHC) and trkB(PLC/PLC)); hippocampal LTP recordings; BDNF stimulation of primary neurons with Western blot readouts for MAPK, CREB, and CaMKIV phosphorylation Neuron High 12367511
2004 TrkB suppresses anoikis (detachment-induced apoptosis) in non-malignant epithelial cells by activating the PI3K/Akt pathway, enabling cells to survive and proliferate in suspension and form metastatic tumors in mice Genome-wide functional anoikis-suppression screen; stable TrkB overexpression in rat intestinal epithelial cells; PI3K inhibitor experiments; mouse subcutaneous and metastasis models Nature High 15329723
2007 TrkB kinase activity (not its extracellular adhesion domains) is necessary and sufficient for anoikis suppression, tumor formation, and experimental metastasis Structure-function analysis with kinase-dead and extracellular domain mutants of TrkB; anoikis assays; mouse tumor and metastasis models Cancer research High 17616679
2010 TrkB-dependent activation of PLCγ1 (via Y816) is a key signaling mechanism for limbic epileptogenesis; trkB(PLC/PLC) mice show reduced PLCγ1 activation in hippocampus and inhibited kindling epileptogenesis, and impaired mossy fiber LTP trkB(PLC/PLC) knock-in mice (Y816F mutation); pilocarpine and kindling epilepsy models; biochemical assays for TrkB and PLCγ1 activation; LTP recordings in hippocampal slices The Journal of neuroscience High 20445044
2001 Truncated TrkB.T1 acts as a dominant-negative inhibitor of full-length TrkB.TK+ by directly co-immunoprecipitating with TrkB.TK+ and inhibiting its autophosphorylation, rather than by sequestering BDNF PC12 cells stably expressing TrkB.TK+ and TrkB.T1; BDNF neutralizing antibody; co-immunoprecipitation; survival assays; tyrosine kinase inhibitor K252a comparison Biochemical and biophysical research communications Medium 11162678
2006 The Y722C missense mutation in NTRK2 impairs BDNF-induced activation of MAPK, PLCγ, and Akt, and reduces BDNF-induced neurite outgrowth and cell survival in PC12 cells Stable transfection of wild-type and mutant TrkB constructs in PC12 cells; Western blot for phospho-MAPK, phospho-PLCγ, phospho-Akt; neurite outgrowth and cell survival assays International journal of obesity Medium 16702999
2010 N-acetylserotonin (NAS) rapidly activates TrkB (but not TrkA or TrkC) in a neurotrophin- and MT3 receptor-independent manner, and exerts antidepressant behavioral effects in a TrkB-dependent way; TrkB activation by NAS occurs in a circadian rhythm in mice TrkB phosphorylation assays in cell lines and mouse brain; BDNF knockout mice; pharmacological receptor blockade; behavioral tests with TrkB-dependent rescue Proceedings of the National Academy of Sciences of the United States of America Medium 20133677
2010 Src family kinases (SFKs) and TrkB mutually regulate each other: zinc transactivates TrkB via SFK-dependent, TrkB-kinase-independent phosphorylation of Tyr-705/706, whereas BDNF activates TrkB independently of SFKs yet subsequently activates SFKs, which in turn regulate BDNF-induced TrkB Tyr-705/706 phosphorylation Biochemical, pharmacological (SFK inhibitors), and chemical-genetic studies of cultured rodent neurons; phospho-specific antibodies for TrkB Tyr-705/706; zinc vs. BDNF stimulation comparison The Journal of biological chemistry Medium 20064930
2015 Slitrk5 directly interacts with TrkB and mediates BDNF-dependent TrkB receptor recycling to Rab11-positive recycling endosomes via Rab11-FIP3; in the absence of Slitrk5, TrkB has reduced ligand-dependent recycling and altered BDNF responsiveness Co-IP; structured illumination microscopy; Slitrk5 KO mice; BDNF stimulation assays; Rab11-FIP3 interaction studies Developmental cell High 26004511
2016 During structural LTP in single dendritic spines of CA1 neurons, NMDAR and CaMKII activation triggers postsynaptically synthesized BDNF release from stimulated spines, leading to autocrine TrkB activation on those same spines; this TrkB activation is required for both structural and functional LTP FRET-based TrkB sensor with two-photon FLIM in cultured hippocampal slices; superecliptic pHluorin-BDNF for release imaging; electron microscopy for postsynaptic BDNF localization; pharmacological inhibition of NMDAR, CaMKII, TrkB Nature High 27680698
2021 Antidepressants (both typical and fast-acting, including ketamine and fluoxetine) directly bind to the transmembrane domain of TrkB dimers at a cholesterol-sensing site, facilitating synaptic localization of TrkB and its activation by BDNF; mutation of the antidepressant-binding motif impairs antidepressant cellular, behavioral, and plasticity responses Atomistic molecular dynamics simulations; radiolabeled drug-binding assays; TrkB transmembrane domain mutagenesis; in vitro signaling assays; behavioral tests in mice; plasticity measurements Cell High 33606976
2023 Psychedelics (LSD, psilocin) bind directly to TrkB at a site within the transmembrane domain of TrkB dimers that partially overlaps with but is distinct from the antidepressant-binding site, with ~1000-fold higher affinity than other antidepressants; their neurotrophic, plasticity, and antidepressant-like effects depend on TrkB binding and BDNF promotion but are independent of 5-HT2A activation Radioligand binding assays; atomistic MD simulations; TrkB mutagenesis; in vitro signaling; mouse behavioral tests; 5-HT2A receptor KO and pharmacological dissection Nature neuroscience High 37280397
2021 Ketamine's rapid antidepressant-induced synaptic potentiation requires postsynaptic TrkB in CA1 neurons (not presynaptic); BDNF from either CA3 or CA1 is required; ketamine activates TrkB via a dynamin1-dependent mechanism Region-specific Cre-mediated deletion of BDNF in CA3 or CA1 and TrkB in CA1 of the Schaffer collateral pathway; hippocampal slice electrophysiology; behavioral antidepressant tests Cell reports High 34407417
2020 Protein tyrosine phosphatase σ (PTPσ/PTPRS), a CSPG receptor, physically interacts with TRKB and restricts TRKB phosphorylation; fluoxetine disrupts the TRKB-PTPσ interaction by binding to the TRKB transmembrane domain, thereby increasing TRKB phosphorylation and reopening critical period-like plasticity in parvalbumin interneurons Co-IP of TRKB and PTPσ; PTPσ-knockout mice; cortical neuron cultures with aggrecan and chABC treatment; ocular dominance plasticity assay; PV-specific TRKB deletion mice The Journal of neuroscience High 33293360
2003 Calcium entry through voltage-gated Ca2+ channels following neuronal depolarization selectively increases full-length (catalytic) TrkB expression via activation of Ca2+-responsive CRE sites in the downstream TrkB promoter P2, while inhibiting the upstream promoter P1 Cultured mouse cortical neurons; Northern blot; RT-PCR; transient transfection of TRKB promoter-luciferase constructs; pharmacological Ca2+ channel blockade The Journal of biological chemistry Medium 12900419
1999 The mouse trkB gene is transcribed from two alternative promoters, P1 and P2; P2 is located within an intron of P1-derived transcripts; both promoters can generate kinase-containing and truncated TrkB isoforms by alternative splicing, with no linkage between promoter usage and splice outcome Deletion analysis with reporter gene transfection; RNase protection mapping; RT-PCR from various tissues Biochimica et biophysica acta Medium 10395916
2006 Dok5 interacts with TrkB (and TrkC) through its PTB domain binding to the TrkB NPQY motif in a kinase-activity-dependent manner, competing with N-Shc for the same binding site, and is involved in neurotrophin-induced MAPK pathway activation Yeast two-hybrid; GST pull-down; co-immunoprecipitation; co-localization in differentiated PC12 cells; mutational analysis; competition assay with N-Shc Cellular signalling Medium 16647839
2008 TrkB interacts with ephrinA5 via its second cysteine-rich domain (CC2) in cis on retinal ganglion cell axons; this interaction augments BDNF-promoted axon branching (in absence of EphA7-Fc), whereas EphA7-Fc activation suppresses branching; the TrkB-ephrinA interaction specifically potentiates the PI3K/Akt pathway Co-IP; overexpression of isolated TrkB-CC2 domain; TrkB RNAi knockdown; axon branching assays; PI3K/Akt pathway analysis; hippocampal synapse formation assays The Journal of neuroscience Medium 19036963
2012 TrkB serves as a synaptic tag: weak theta-burst stimulation transiently activates TrkB in stimulated synapses in a protein-synthesis-independent manner, and this TrkB activation is required for converting early-LTP to late-LTP by capturing plasticity-related proteins; behaviorally, TrkB inhibition during weak training blocks consolidation of short-term into long-term memory Electrophysiological LTP recordings in hippocampal slices; pharmacological TrkB inhibition; in vivo behavioral memory consolidation tests The Journal of neuroscience Medium 21849537
2014 Neuronal activity converts BDNF-TrkB signaling from transient to sustained mode via Ca2+ elevation and CaMKII activation that increases surface TrkB expression; sustained TrkB signaling facilitates dendritic branching and rescues glutamate-induced apoptosis KCl depolarization and theta-burst stimulation of cultured neurons; Western blot for phospho-TrkB kinetics; surface TrkB quantification; CaMKII inhibition; dendritic branching and survival assays Journal of cell science Medium 24634513
2022 Senescent cells upregulate TrkB (NTRK2) and secrete BDNF as a SASP factor; autocrine BDNF-TrkB signaling activates ERK5 and elevates BCL2L2, promoting senescent cell survival; TrkB inhibition selectively triggers apoptosis of senescent cells and reduces their accumulation in aged mouse organs Drug library screen; TrkB KO and BDNF knockdown in senescent cells; Western blot for ERK5, BCL2L2; apoptosis assays; TrkB inhibitor treatment of aged mice with organ analysis Nature communications Medium 36266274
2015 BDNF acting on the truncated TrkB.T1 receptor in astrocytes inhibits GlyT1 and GlyT2 glycine transporter activity by promoting transporter internalization via a Rho GTPase-dependent (Rho family toxin B-sensitive) mechanism, independent of PLCγ, PI3K, or MAPK pathways Radiolabeled glycine uptake assays; Vmax/Km determination; dynasore (endocytosis inhibitor); pathway inhibitors (PLCγ, PI3K, MAPK); Rho family toxin B; TrkB-T1 shRNA knockdown; immunofluorescence Glia Medium 26200505
2019 TrkB signaling in astrocytic TrkB.T1 is required for astrocyte morphological maturation; deletion of TrkB.T1 (globally or astrocyte-specifically) produces morphologically immature astrocytes with reduced volume, dysregulated perisynaptic gene expression, and failure to support normal excitatory synaptogenesis Global and astrocyte-specific TrkB.T1 conditional knockout mice; astrocyte volume measurements; RNA-seq; synaptogenesis co-culture assays; novel astrocyte culture paradigm with BDNF treatment eLife High 31433295
2014 Oocyte-specific deletion of Ntrk2 causes post-pubertal oocyte death and infertility; NTRK2 mediates gonadotropin-induced PI3K-Akt survival signaling in oocytes; puberty-induced NTRK2.FL expression in oocytes requires concurrent BDNF and kisspeptin (via granulosa-cell-produced KISS1R) signaling Oocyte-specific Ntrk2 conditional KO mice; Western blot for PI3K/Akt activation; cell line co-expression of NTRK2.T1 and KISS1R; BDNF and kisspeptin stimulation assays Endocrinology Medium 24877631
2012 Calpain processing of full-length TrkB-FL during excitotoxicity produces a truncated protein lacking the tyrosine kinase domain, similar to TrkB-T1; coincident upregulation of TrkB-T1 mRNA creates an imbalance favoring kinase-inactive TrkB and contributing to neuronal death; restoring TrkB-FL/TrkB-T1 balance via lentiviral intervention rescues neurons from excitotoxic death In vitro excitotoxicity models; calpain inhibitors; Western blot; mRNA quantification; lentiviral co-delivery of TrkB-T1 shRNA and TrkB-FL; stroke patient tissue analysis Cell death & disease Medium 22258407
2020 A truncated kinase-deficient NTRK2 splice variant (TrkB.T1) enhances PDGF-driven glioma in vivo and augments PDGF-induced Akt and STAT3 signaling in vitro through PI3K signaling cascades in a ligand-independent fashion In vivo PDGF-driven glioma mouse model; in vitro signaling assays (Western blot for pAkt, pSTAT3); next-generation sequencing; PI3K pathway analysis Nature communications Medium 32532995
1994 BDNF induces tyrosine phosphorylation of TrkB and downstream phosphorylation of PLCγ1, ERK1/2, and PI3K in neuroblastoma cells; BDNF/TrkB signaling promotes cell survival and neurite outgrowth in an autocrine/paracrine manner BDNF stimulation of SMS-KCN neuroblastoma cells; immunoprecipitation and Western blot for phospho-TrkB, phospho-PLCγ1, phospho-ERK1/2, PI3K; cell survival and neurite outgrowth assays; immediate-early gene expression Molecular and cellular biology High 8264643

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 TrkB signalling pathways in LTP and learning. Nature reviews. Neuroscience 837 19927149
2013 Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nature genetics 640 23817572
2010 Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Developmental neurobiology 561 20186705
2021 Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell 501 33606976
2004 Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature 487 15329723
2000 Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Investigative ophthalmology & visual science 437 10711692
2002 Mechanism of TrkB-mediated hippocampal long-term potentiation. Neuron 374 12367511
1994 Expression and function of TRK-B and BDNF in human neuroblastomas. Molecular and cellular biology 343 8264643
2023 Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature neuroscience 319 37280397
2016 Autocrine BDNF-TrkB signalling within a single dendritic spine. Nature 260 27680698
1998 TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections. The Journal of neuroscience : the official journal of the Society for Neuroscience 207 9736654
2013 TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. International journal of molecular sciences 198 23670594
2010 N-acetylserotonin activates TrkB receptor in a circadian rhythm. Proceedings of the National Academy of Sciences of the United States of America 168 20133677
2012 Truncated TrkB: beyond a dominant negative receptor. Cytokine & growth factor reviews 165 22341689
2016 Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration. International journal of molecular sciences 156 27657046
2019 Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1. eLife 145 31433295
2009 Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Molecular psychiatry 136 19844206
2011 The CREB1-BDNF-NTRK2 pathway in depression: multiple gene-cognition-environment interactions. Biological psychiatry 131 21215389
2008 A TrkB/EphrinA interaction controls retinal axon branching and synaptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 130 19036963
2012 A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 22302819
2005 A neurotrophin axis in myeloma: TrkB and BDNF promote tumor-cell survival. Blood 125 15657181
1997 Expression of TrkA, TrkB and TrkC in human neuroblastomas. Journal of neuro-oncology 120 9049830
2001 Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival. Biochemical and biophysical research communications 113 11162678
2005 Biological effects of TrkA and TrkB receptor signaling in neuroblastoma. Cancer letters 100 15921851
1996 Expression and function of TrkB variants in developing sensory neurons. The EMBO journal 99 8978665
2011 TrkB as a potential synaptic and behavioral tag. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 21849537
1993 BDNF and trkB mRNA expression in the hippocampal formation of aging rats. Neurobiology of aging 91 8487914
2012 BDNF-TrkB signaling and neuroprotection in schizophrenia. Asian journal of psychiatry 90 23380313
2018 Targeting the BDNF/TrkB pathway for the treatment of tumors. Oncology letters 84 30675270
2007 Critical role for TrkB kinase function in anoikis suppression, tumorigenesis, and metastasis. Cancer research 81 17616679
2012 Imbalance of neurotrophin receptor isoforms TrkB-FL/TrkB-T1 induces neuronal death in excitotoxicity. Cell death & disease 80 22258407
2021 A synaptic locus for TrkB signaling underlying ketamine rapid antidepressant action. Cell reports 78 34407417
2015 Slitrk5 Mediates BDNF-Dependent TrkB Receptor Trafficking and Signaling. Developmental cell 77 26004511
2006 Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesity. International journal of obesity (2005) 76 16702999
2020 Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain. Cells 75 32403409
2010 BDNF and TrkB in neuronal differentiation of Fmr1-knockout mouse. Neurobiology of disease 73 21047554
2019 Targeting BDNF/TrkB pathways for preventing or suppressing epilepsy. Neuropharmacology 72 31377199
2017 Therapeutic Potentials of BDNF/TrkB in Breast Cancer; Current Status and Perspectives. Journal of cellular biochemistry 72 28230291
2014 Neurotrophin receptor TrkB promotes lung adenocarcinoma metastasis. Proceedings of the National Academy of Sciences of the United States of America 70 24982195
2007 TrkB agonists ameliorate obesity and associated metabolic conditions in mice. Endocrinology 70 18063676
1996 Expression of TrkB receptor isoforms in the developing avian visual system. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 8774442
2010 Overexpression of BDNF and TrkB in human bladder cancer specimens. Oncology reports 68 20878119
2017 Isoflurane produces antidepressant effects and induces TrkB signaling in rodents. Scientific reports 65 28798343
2014 Loss of Ntrk2/Kiss1r signaling in oocytes causes premature ovarian failure. Endocrinology 65 24877631
2014 BDNF and its TrkB receptor in human fracture healing. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 65 24984919
2013 Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders. Cerebral cortex (New York, N.Y. : 1991) 64 23960204
2009 NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary. Reproduction (Cambridge, England) 64 19357131
2005 The neurotrophic receptor TrkB in anoikis resistance and metastasis: a perspective. Cancer research 63 16103047
2008 Genetic association of neurotrophic tyrosine kinase receptor type 2 (NTRK2) With Alzheimer's disease. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 61 17918233
2016 PI3K and MAPK pathways mediate the BDNF/TrkB-increased metastasis in neuroblastoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 60 27752996
2007 Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biological psychiatry 60 17884018
2010 Disruption of TrkB-mediated phospholipase Cgamma signaling inhibits limbic epileptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 20445044
2008 Association studies of the BDNF and the NTRK2 gene polymorphisms with prophylactic lithium response in bipolar patients. Pharmacogenomics 59 19018715
2016 Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways. Molecular nutrition & food research 58 27735126
2015 Norepinephrine Protects against Amyloid-β Toxicity via TrkB. Journal of Alzheimer's disease : JAD 58 25208620
2022 TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions. Frontiers in neuroscience 55 35321093
2010 Mutual regulation of Src family kinases and the neurotrophin receptor TrkB. The Journal of biological chemistry 55 20064930
2003 Ca(2+)-dependent regulation of TrkB expression in neurons. The Journal of biological chemistry 55 12900419
2020 Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities. Scientific reports 53 32493978
2014 Neuronal activity alters BDNF-TrkB signaling kinetics and downstream functions. Journal of cell science 51 24634513
2004 Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory. Drug news & perspectives 49 15514702
2021 The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases. Life (Basel, Switzerland) 44 33477900
2020 Chondroitinase and Antidepressants Promote Plasticity by Releasing TRKB from Dephosphorylating Control of PTPσ in Parvalbumin Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 33293360
2020 A kinase-deficient NTRK2 splice variant predominates in glioma and amplifies several oncogenic signaling pathways. Nature communications 42 32532995
2012 Prelimbic BDNF and TrkB signaling regulates consolidation of both appetitive and aversive emotional learning. Translational psychiatry 42 23250006
2015 BDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytes. Glia 41 26200505
2014 BDNF deletion or TrkB impairment in amygdala inhibits both appetitive and aversive learning. The Journal of neuroscience : the official journal of the Society for Neuroscience 40 24523535
2019 Isoflurane produces antidepressant effects inducing BDNF-TrkB signaling in CUMS mice. Psychopharmacology 38 31197433
2018 Prefrontal cortical trkB, glucocorticoids, and their interactions in stress and developmental contexts. Neuroscience and biobehavioral reviews 38 30477984
2022 A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin. Nature communications 37 35973996
2015 Role of TrkB kinase activity in aging diaphragm neuromuscular junctions. Experimental gerontology 36 26517952
2012 RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB. Molecular pharmacology 36 22752556
2014 The brain-uterus connection: brain derived neurotrophic factor (BDNF) and its receptor (Ntrk2) are conserved in the mammalian uterus. PloS one 35 24714156
2008 Targeting TrkB neurotrophin receptor to treat depression. Expert opinion on therapeutic targets 34 18479217
2022 The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish. International journal of molecular sciences 33 35269763
2017 Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure. PLoS biology 33 29186135
2015 TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression. Molecules and cells 33 26657794
2013 The interaction of BDNF and NTRK2 gene increases the susceptibility of paranoid schizophrenia. PloS one 32 24069289
1998 Expression of the TrkB neurotrophin receptor by thymic macrophages. Immunology 32 9741346
2018 Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway. Behavioural brain research 30 29680784
2022 A BDNF-TrkB autocrine loop enhances senescent cell viability. Nature communications 29 36266274
2022 The MBNL1/circNTRK2/PAX5 pathway regulates aerobic glycolysis in glioblastoma cells by encoding a novel protein NTRK2-243aa. Cell death & disease 28 36064939
2020 Cholinergic neuroplasticity in asthma driven by TrkB signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28 32277855
2021 ERRγ ligand HPB2 upregulates BDNF-TrkB and enhances dopaminergic neuronal phenotype. Pharmacological research 27 33434621
2021 Inhibiting BDNF/TrkB.T1 receptor improves resiniferatoxin-induced postherpetic neuralgia through decreasing ASIC3 signaling in dorsal root ganglia. Journal of neuroinflammation 27 33874962
2020 LMP1 promotes nasopharyngeal carcinoma metastasis through NTRK2-mediated anoikis resistance. American journal of cancer research 26 32775002
2018 Partial TrkB receptor activation suppresses cortical epileptogenesis through actions on parvalbumin interneurons. Neurobiology of disease 26 29408225
2011 Expression of TrkB and BDNF in human cochlea-an immunohistochemical study. Cell and tissue research 26 21739244
1999 The mouse neurotrophin receptor trkB gene is transcribed from two different promoters. Biochimica et biophysica acta 26 10395916
2014 The truncated TrkB receptor influences mammalian sleep. American journal of physiology. Regulatory, integrative and comparative physiology 25 25502751
2022 Enhanced BDNF and TrkB Activation Enhance GABA Neurotransmission in Cerebellum in Hyperammonemia. International journal of molecular sciences 23 36233065
2020 Individual differences in stereotypy and neuron subtype translatome with TrkB deletion. Molecular psychiatry 23 32366954
2006 Dok5 is substrate of TrkB and TrkC receptors and involved in neurotrophin induced MAPK activation. Cellular signalling 23 16647839
2018 P2X4R silence suppresses glioma cell growth through BDNF/TrkB/ATF4 signaling pathway. Journal of cellular biochemistry 22 30362154
2015 The neurotrophic receptor Ntrk2 directs lymphoid tissue neovascularization during Leishmania donovani infection. PLoS pathogens 22 25710496
2007 Implications of tropomyosin-related kinase B (TrkB) in head and neck cancer. Anticancer research 22 17970052
2017 TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway. Oncotarget 21 29312563
2014 Downregulated GABA and BDNF-TrkB pathway in chronic cyclothiazide seizure model. Neural plasticity 21 24757570
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2014 Antiseizure effects of TrkB kinase inhibition. Epilepsia 20 24903749