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Gene Review

Ntrk2  -  neurotrophic tyrosine kinase, receptor,...

Mus musculus

Synonyms: AI848316, BDNF/NT-3 growth factors receptor, C030027L06Rik, GP145-TrkB/GP95-TrkB, Neurotrophic tyrosine kinase receptor type 2, ...
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Disease relevance of Ntrk2


Psychiatry related information on Ntrk2

  • We asked whether this exuberance is attributable to abnormal TrkB signaling, because modulation of TrkB signaling during a critical period dramatically influences the segregation and the morphology of TCAs in layer IV of the visual cortex [7].

High impact information on Ntrk2


Chemical compound and disease context of Ntrk2


Biological context of Ntrk2

  • Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo [11].
  • However, in double mutant mice, we now show that reducing the expression of both TrkB and TrkC causes massive cell death of postnatal hippocampal and cerebellar granule neurons [14].
  • Experiments in cell culture have revealed that an intact Shc adaptor binding site on TrkB and subsequent activation of the Ras/MAPK pathway are important for neuronal survival and neurite outgrowth [15].
  • Ts16 neurons have normal levels of the TrkB tyrosine kinase receptor but an upregulation of the TrkB.T1 truncated receptor isoform [16].
  • Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses [15].

Anatomical context of Ntrk2

  • Finally, mice with a disrupted Ntrk2 gene lacked a significant proportion of their intramyocardial blood vessels [4].
  • Furthermore, the BDNF dose dependency displayed by these TrkB-expressing fibroblasts is similar to that required to support the survival of primary neurons [17].
  • Correlating with the loss of granule cells, the number of mossy fibers projecting to CA3 pyramidal neurons was markedly reduced in mice carrying mutant trkB/trkC alleles, demonstrating impairment of excitatory pathways in the hippocampus [14].
  • Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons [18].
  • Kinetic analysis of neuronal death in the hippocampus showed that dentate gyrus granule neurons become dependent on TrkB and TrkC after the first postnatal week, shortly after the period of naturally occurring cell death, indicating a role of these receptors in supporting postmitotic neurons [14].

Associations of Ntrk2 with chemical compounds

  • Postsynaptic glutamate receptors are not affected by TrkB reduction, indicating that BDNF does not modulate plasticity through postsynaptic TrkB [19].
  • First, each of the high-affinity tyrosine kinase receptors, trkA, trkB, and trkC, as well as the low-affinity p75 receptor has an impact on at least one type of mechanoreceptor [20].
  • TrkB receptors mediate the effects of BDNF on striatal medium spiny neurons and mesencephalic dopamine neurons [21].
  • Interactions between TrkB signaling and serotonin excess in the developing murine somatosensory cortex: a role in tangential and radial organization of thalamocortical axons [7].
  • TrkB variants with deletions in the leucine-rich motifs of the extracellular domain [22].
  • Brain monoamines seem to be critical mediators of antidepressant-induced TrkB activation, as antidepressants reboxetine and citalopram do not produce TrkB activation in the brains of serotonin- or norepinephrine-depleted mice [23].

Physical interactions of Ntrk2

  • Surprisingly, most sets of trkA-dependent sensory innervation are suppressed by trkB perhaps interacting with p75 [24].
  • A series of mutants with deletion in the extracellular portion of TrkB were expressed transiently and stably in mammalian cells to examine the brain-derived neurotrophic factor (BDNF)-binding properties of TrkB [25].

Co-localisations of Ntrk2


Regulatory relationships of Ntrk2

  • Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra [27].
  • Activation of Wt1 in an inducible cell line significantly enhanced TrkB expression [4].
  • We find that increases in cAMP can rapidly activate the BDNF receptor TrkB and induce BDNF-dependent long-lasting potentiation at the Schaffer collateral-CA1 synapse in hippocampus [28].
  • Exposure of mature cortical cultures for 48 h to NT-4/5 induced neuronal death through TrkB activation [29].
  • TrkB-expressing cells were located above the NeuroD-positive layer in the middle compartment [30].

Other interactions of Ntrk2

  • In the present paper, we use antibodies to TrkA, TrkB, and TrkC to characterize their expression patterns and to determine which subpopulations of cells are lost in mice lacking individual neurotrophins or Trk receptors [31].
  • Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo [31].
  • In the inner ear, TrkB- and TrkC-dependent neurons were shown to at least partially depend on each other for survival, most likely indirectly due to abnormal development of their common targets [32].
  • Our results suggest that signaling via TrkA, but not TrkB, may be involved in the postnatal regulation of AChE activity in the adrenal medulla and its preganglionic nerves [33].
  • We conclude that impairment in trkB and/or trkC signaling induces a phenotype in the aged SN, which includes two hallmarks of PD, losses of TH positive neurons and axons along with massive neuronal deposits of alpha-synuclein [27].

Analytical, diagnostic and therapeutic context of Ntrk2


  1. A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control. Botchkarev, V.A., Botchkareva, N.V., Welker, P., Metz, M., Lewin, G.R., Subramaniam, A., Bulfone-Paus, S., Hagen, E., Braun, A., Lommatzsch, M., Renz, H., Paus, A.R. FASEB J. (1999) [Pubmed]
  2. BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development. Agerman, K., Hjerling-Leffler, J., Blanchard, M.P., Scarfone, E., Canlon, B., Nosrat, C., Ernfors, P. Development (2003) [Pubmed]
  3. Involvement of a spinal brain-derived neurotrophic factor/full-length TrkB pathway in the development of nerve injury-induced thermal hyperalgesia in mice. Yajima, Y., Narita, M., Narita, M., Matsumoto, N., Suzuki, T. Brain Res. (2002) [Pubmed]
  4. Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1. Wagner, N., Wagner, K.D., Theres, H., Englert, C., Schedl, A., Scholz, H. Genes Dev. (2005) [Pubmed]
  5. Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Gonzalez, M., Ruggiero, F.P., Chang, Q., Shi, Y.J., Rich, M.M., Kraner, S., Balice-Gordon, R.J. Neuron (1999) [Pubmed]
  6. TrkB agonists ameliorate obesity and associated metabolic conditions in mice. Tsao, D., Thomsen, H.K., Chou, J., Stratton, J., Hagen, M., Loo, C., Garcia, C., Sloane, D.L., Rosenthal, A., Lin, J.C. Endocrinology (2008) [Pubmed]
  7. Interactions between TrkB signaling and serotonin excess in the developing murine somatosensory cortex: a role in tangential and radial organization of thalamocortical axons. Vitalis, T., Cases, O., Gillies, K., Hanoun, N., Hamon, M., Seif, I., Gaspar, P., Kind, P., Price, D.J. J. Neurosci. (2002) [Pubmed]
  8. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Jones, K.R., Fariñas, I., Backus, C., Reichardt, L.F. Cell (1994) [Pubmed]
  9. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Klein, R., Smeyne, R.J., Wurst, W., Long, L.K., Auerbach, B.A., Joyner, A.L., Barbacid, M. Cell (1993) [Pubmed]
  10. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Klein, R., Conway, D., Parada, L.F., Barbacid, M. Cell (1990) [Pubmed]
  11. Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Conover, J.C., Erickson, J.T., Katz, D.M., Bianchi, L.M., Poueymirou, W.T., McClain, J., Pan, L., Helgren, M., Ip, N.Y., Boland, P. Nature (1995) [Pubmed]
  12. Unliganded c-erbA/thyroid hormone receptor induces trkB expression in neuroblastoma cells. Pastor, R., Bernal, J., Rodríguez-Peña, A. Oncogene (1994) [Pubmed]
  13. Correlated long-term increase of brain-derived neurotrophic factor and Trk B proteins in enlarged granule cells of mouse hippocampus after kainic acid injection. Inoue, T., Hirai, H., Onteniente, B., Suzuki, F. Neuroscience (1998) [Pubmed]
  14. TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Minichiello, L., Klein, R. Genes Dev. (1996) [Pubmed]
  15. Point mutation in trkB causes loss of NT4-dependent neurons without major effects on diverse BDNF responses. Minichiello, L., Casagranda, F., Tatche, R.S., Stucky, C.L., Postigo, A., Lewin, G.R., Davies, A.M., Klein, R. Neuron (1998) [Pubmed]
  16. In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues neuronal cell death in a trisomic mouse model. Dorsey, S.G., Renn, C.L., Carim-Todd, L., Barrick, C.A., Bambrick, L., Krueger, B.K., Ward, C.W., Tessarollo, L. Neuron (2006) [Pubmed]
  17. TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor. Glass, D.J., Nye, S.H., Hantzopoulos, P., Macchi, M.J., Squinto, S.P., Goldfarb, M., Yancopoulos, G.D. Cell (1991) [Pubmed]
  18. Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons. Postigo, A., Calella, A.M., Fritzsch, B., Knipper, M., Katz, D., Eilers, A., Schimmang, T., Lewin, G.R., Klein, R., Minichiello, L. Genes Dev. (2002) [Pubmed]
  19. The role of brain-derived neurotrophic factor receptors in the mature hippocampus: modulation of long-term potentiation through a presynaptic mechanism involving TrkB. Xu, B., Gottschalk, W., Chow, A., Wilson, R.I., Schnell, E., Zang, K., Wang, D., Nicoll, R.A., Lu, B., Reichardt, L.F. J. Neurosci. (2000) [Pubmed]
  20. Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Fundin, B.T., Silos-Santiago, I., Ernfors, P., Fagan, A.M., Aldskogius, H., DeChiara, T.M., Phillips, H.S., Barbacid, M., Yancopoulos, G.D., Rice, F.L. Dev. Biol. (1997) [Pubmed]
  21. BDNF heterozygous mice demonstrate age-related changes in striatal and nigral gene expression. Saylor, A.J., Meredith, G.E., Vercillo, M.S., Zahm, D.S., McGinty, J.F. Exp. Neurol. (2006) [Pubmed]
  22. TrkB variants with deletions in the leucine-rich motifs of the extracellular domain. Ninkina, N., Grashchuck, M., Buchman, V.L., Davies, A.M. J. Biol. Chem. (1997) [Pubmed]
  23. Pharmacologically diverse antidepressants rapidly activate brain-derived neurotrophic factor receptor TrkB and induce phospholipase-Cgamma signaling pathways in mouse brain. Rantamäki, T., Hendolin, P., Kankaanpää, A., Mijatovic, J., Piepponen, P., Domenici, E., Chao, M.V., Männistö, P.T., Castrén, E. Neuropsychopharmacology (2007) [Pubmed]
  24. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Rice, F.L., Albers, K.M., Davis, B.M., Silos-Santiago, I., Wilkinson, G.A., LeMaster, A.M., Ernfors, P., Smeyne, R.J., Aldskogius, H., Phillips, H.S., Barbacid, M., DeChiara, T.M., Yancopoulos, G.D., Dunne, C.E., Fundin, B.T. Dev. Biol. (1998) [Pubmed]
  25. TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor. Kojima, S., Nakayama, T., Kuwajima, G., Suzuki, H., Sakata, T. Biochim. Biophys. Acta (1999) [Pubmed]
  26. BDNF/NT4-5 receptor TrkB and cadherin participate in cell-cell adhesion. Zhou, H., Welcher, A.A., Shooter, E.M. J. Neurosci. Res. (1997) [Pubmed]
  27. Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra. von Bohlen und Halbach, O., Minichiello, L., Unsicker, K. FASEB J. (2005) [Pubmed]
  28. Some forms of cAMP-mediated long-lasting potentiation are associated with release of BDNF and nuclear translocation of phospho-MAP kinase. Patterson, S.L., Pittenger, C., Morozov, A., Martin, K.C., Scanlin, H., Drake, C., Kandel, E.R. Neuron (2001) [Pubmed]
  29. NR2A induction and NMDA receptor-dependent neuronal death by neurotrophin-4/5 in cortical cell culture. Choi, S.Y., Hwang, J.J., Koh, J.Y. J. Neurochem. (2004) [Pubmed]
  30. Quantitative analysis of expression of NeuroD, GAP43 and receptor tyrosine kinase B in developing mouse olfactory neuroepithelium. Yasui, R., Hasegawa, M., Doi, K., Shimizu, K., Ohtuski, N., Ishida, H., Nibu, K. Acta oto-laryngologica. Supplementum. (2004) [Pubmed]
  31. Characterization of neurotrophin and Trk receptor functions in developing sensory ganglia: direct NT-3 activation of TrkB neurons in vivo. Fariñas, I., Wilkinson, G.A., Backus, C., Reichardt, L.F., Patapoutian, A. Neuron (1998) [Pubmed]
  32. Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons. Minichiello, L., Piehl, F., Vazquez, E., Schimmang, T., Hökfelt, T., Represa, J., Klein, R. Development (1995) [Pubmed]
  33. Reduced acetylcholinesterase (AChE) activity in adrenal medulla and loss of sympathetic preganglionic neurons in TrkA-deficient, but not TrkB-deficient, mice. Schober, A., Minichiello, L., Keller, M., Huber, K., Layer, P.G., Roig-López, J.L., García-Arrarás, J.E., Klein, R., Unsicker, K. J. Neurosci. (1997) [Pubmed]
  34. Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at later stages of cerebellar granule cell differentiation. Gao, W.Q., Zheng, J.L., Karihaloo, M. J. Neurosci. (1995) [Pubmed]
  35. Embryonic precursor cells that express Trk receptors: induction of different cell fates by NGF, BDNF, NT-3, and CNTF. Lachyankar, M.B., Condon, P.J., Quesenberry, P.J., Litofsky, N.S., Recht, L.D., Ross, A.H. Exp. Neurol. (1997) [Pubmed]
  36. Expression of BDNF and TrkB in mouse taste buds after denervation and in circumvallate papillae during development. Uchida, N., Kanazawa, M., Suzuki, Y., Takeda, M. Arch. Histol. Cytol. (2003) [Pubmed]
  37. Signal transduction events mediated by the BDNF receptor gp 145trkB in primary hippocampal pyramidal cell culture. Marsh, H.N., Scholz, W.K., Lamballe, F., Klein, R., Nanduri, V., Barbacid, M., Palfrey, H.C. J. Neurosci. (1993) [Pubmed]
  38. Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression. Endres, M., Fan, G., Hirt, L., Fujii, M., Matsushita, K., Liu, X., Jaenisch, R., Moskowitz, M.A. J. Cereb. Blood Flow Metab. (2000) [Pubmed]
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