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Gene Review

Ntrk3  -  neurotrophic tyrosine kinase, receptor,...

Mus musculus

Synonyms: AW125844, GP145-TrkC, NT-3 growth factor receptor, Neurotrophic tyrosine kinase receptor type 3, Ntrk3_tv3, ...
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Disease relevance of Ntrk3


Psychiatry related information on Ntrk3


High impact information on Ntrk3

  • Peripheral neuronal subpopulations expressing the TrkC receptor tyrosine kinase respond to Nt3 with enhanced survival, mitogenesis or cell migration and these neurons are lost in homozygous Nt3 null (-/-) mutant mice [8].
  • These mice display abnormal movements and postures, indicating that NT3/TrkC-dependent sensor; neurons may play a primary role in proprioception, the sense of position and movement of the limbs [9].
  • Here we show that homozygous mice defective for TrkC tyrosine protein kinase receptors lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord [9].
  • One of these isoforms, gp145trkC/TrkC K1, mediates the trophic properties of NT3 in cultured cells [9].
  • TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons [10].

Chemical compound and disease context of Ntrk3

  • To test whether these isoforms have different functions related to axon outgrowth, full-length or tyrosine kinase-lacking TrkC receptors were overexpressed in embryonic dorsal root ganglion neurons maintained in explant cultures in neurotrophin-3 (NT-3)-containing media [11].

Biological context of Ntrk3


Anatomical context of Ntrk3

  • Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development [14].
  • We obtained the same results with Cos-7 cells expressing TrkC [12].
  • 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 [15].
  • 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 [10].
  • Mice lacking neurotrophin-3 (NT-3) or its receptor, TrkC, lose many spiral ganglion cells predominantly in the basal turn of the cochlea [16].

Associations of Ntrk3 with chemical compounds

  • When neuroblasts migrated and differentiated, immunostaining was used for locating NT3 and TrkC in the morphogenetic sequence, bromodeoxyuridine for proliferation, and synaptic vesicle protein for synaptogenesis [17].
  • Experiments with the use of cell-permeant inhibitors argue against a major role for PLC gamma and PtdIns 3-kinase in the activation of MAPK by TrkC [18].

Physical interactions of Ntrk3


Regulatory relationships of Ntrk3

  • In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal noggin-overexpressing animals, again an effect detectable at E18 [19].
  • Our results show that myelin formation is inhibited in the absence of functional p75NTR and enhanced by blocking TrkC activity [20].
  • TrkA neurons expressing TrkC-reporter range from small to large size and supply well-defined types of mystacial pad innervation [21].
  • Our findings demonstrated that muscle-derived neurotrophin-3 (NT-3) has the unique ability to enhance the aggregation of acetylcholine receptors (AChRs) on the myotubes following co-culture with NG108-15 cells expressing TrkC [22].

Other interactions of Ntrk3

  • Our data confirm an unexpectedly high proportion of sensory neuron losses in NT-3 (>70%), BDNF (>20%), and TrkC (>30%) mutants, which encompass populations thought to be NGF-dependent [23].
  • Its extracellular domain exhibits the same modular structure found in its homologs, TrkA and TrkC, consisting of an N-terminal LRM3 cassette and two immunoglobulin-like modules (Ig2 domain) adjacent to the membrane [24].
  • At the time of birth, however, Merkel cells are immunoreactive for NT-3, TrkC and p75NTR [13].
  • Three mRNAs, Gfra2, TrkA, and TrkC, were differentially expressed [25].
  • In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively [26].

Analytical, diagnostic and therapeutic context of Ntrk3


  1. The Trk family of neurotrophin receptors. Barbacid, M. J. Neurobiol. (1994) [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. Modification of glial-neuronal cell interactions prevents photoreceptor apoptosis during light-induced retinal degeneration. Harada, T., Harada, C., Nakayama, N., Okuyama, S., Yoshida, K., Kohsaka, S., Matsuda, H., Wada, K. Neuron (2000) [Pubmed]
  4. Adenovirus vector-directed expression of the neurotrophin-3 receptor (TrkC) in mouse astrocytes. Rubio, N., Abad-Rodriguez, J. J. Neurovirol. (2001) [Pubmed]
  5. Neurotrophin-3 in the development of the enteric nervous system. Chalazonitis, A. Prog. Brain Res. (2004) [Pubmed]
  6. Dissection of NT3 functions in vivo by gene replacement strategy. Coppola, V., Kucera, J., Palko, M.E., Martinez-De Velasco, J., Lyons, W.E., Fritzsch, B., Tessarollo, L. Development (2001) [Pubmed]
  7. Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reaction. Dierssen, M., Gratac??s, M., Sah??n, I., Mart??n, M., Gallego, X., Amador-Arjona, A., Mart??nez de Lagr??n, M., Murtra, P., Mart??, E., Pujana, M.A., Ferrer, I., Dalf??, E., Mart??nez-Cu??, C., Fl??rez, J., Torres-Peraza, J.F., Alberch, J., Maldonado, R., Fillat, C., Estivill, X. Neurobiol. Dis. (2006) [Pubmed]
  8. Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development. Donovan, M.J., Hahn, R., Tessarollo, L., Hempstead, B.L. Nat. Genet. (1996) [Pubmed]
  9. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements. Klein, R., Silos-Santiago, I., Smeyne, R.J., Lira, S.A., Brambilla, R., Bryant, S., Zhang, L., Snider, W.D., Barbacid, M. Nature (1994) [Pubmed]
  10. TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Minichiello, L., Klein, R. Genes Dev. (1996) [Pubmed]
  11. Differential effects of TrkC isoforms on sensory axon outgrowth. Ichinose, T., Snider, W.D. J. Neurosci. Res. (2000) [Pubmed]
  12. Neurotrophin 3 activation of TrkC induces Schwann cell migration through the c-Jun N-terminal kinase pathway. Yamauchi, J., Chan, J.R., Shooter, E.M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  13. Neurotrophin-3 signaling in mammalian Merkel cell development. Szeder, V., Grim, M., Kucera, J., Sieber-Blum, M. Dev. Dyn. (2003) [Pubmed]
  14. Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons. Tessarollo, L., Vogel, K.S., Palko, M.E., Reid, S.W., Parada, L.F. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. 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]
  16. The role of neurotrophic factors in regulating the development of inner ear innervation. Fritzsch, B., Silos-Santiago, I., Bianchi, L.M., Fariñas, I. Trends Neurosci. (1997) [Pubmed]
  17. Site-specific interactions of neurotrophin-3 and fibroblast growth factor (FGF2) in the embryonic development of the mouse cochlear nucleus. Hossain, W.A., D'Sa, C., Morest, D.K. J. Neurobiol. (2006) [Pubmed]
  18. Analysis of mitogen-activated protein kinase activation by naturally occurring splice variants of TrkC, the receptor for neurotrophin-3. Gunn-Moore, F.J., Williams, A.G., Tavaré, J.M. Biochem. J. (1997) [Pubmed]
  19. Bone morphogenetic protein-2 and -4 limit the number of enteric neurons but promote development of a TrkC-expressing neurotrophin-3-dependent subset. Chalazonitis, A., D'Autréaux, F., Guha, U., Pham, T.D., Faure, C., Chen, J.J., Roman, D., Kan, L., Rothman, T.P., Kessler, J.A., Gershon, M.D. J. Neurosci. (2004) [Pubmed]
  20. The neurotrophin receptor p75NTR as a positive modulator of myelination. Cosgaya, J.M., Chan, J.R., Shooter, E.M. Science (2002) [Pubmed]
  21. TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells. Fünfschilling, U., Ng, Y.G., Zang, K., Miyazaki, J., Reichardt, L.F., Rice, F.L. J. Comp. Neurol. (2004) [Pubmed]
  22. Muscle-derived neurotrophin-3 increases the aggregation of acetylcholine receptors in neuron-muscle co-cultures. Fu, A.K., Ip, F.C., Lai, K.O., Tsim, K.W., Ip, N.Y. Neuroreport (1997) [Pubmed]
  23. Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice. Liebl, D.J., Tessarollo, L., Palko, M.E., Parada, L.F. J. Neurosci. (1997) [Pubmed]
  24. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 bind to a single leucine-rich motif of TrkB. Windisch, J.M., Marksteiner, R., Lang, M.E., Auer, B., Schneider, R. Biochemistry (1995) [Pubmed]
  25. Neurotrophic factor receptor expression and in vitro nerve growth of geniculate ganglion neurons that supply divergent nerves. Yamout, A., Spec, A., Cosmano, J., Kashyap, M., Rochlin, M.W. Dev. Neurosci. (2005) [Pubmed]
  26. TRPV2, a capsaicin receptor homologue, is expressed predominantly in the neurotrophin-3-dependent subpopulation of primary sensory neurons. Tamura, S., Morikawa, Y., Senba, E. Neuroscience (2005) [Pubmed]
  27. 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]
  28. Signaling for activity-dependent inhibitory synaptogenesis via the TrkB receptor. Seil, F.J. Exp. Neurol. (2001) [Pubmed]
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