Neurotrophin-3 is a protein that in humans is encoded by the NTF3gene.[5][6]
The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a proteingrowth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 was the third neurotrophic factor to be characterized, after nerve growth factor (NGF) and BDNF (Brain Derived Neurotrophic Factor).[7]
Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis.
NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB).[8][9]
As mentioned above, there are other related Trk receptors, TrkA and TrkB. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
The other NT-3 receptor, the LNGFR, plays a somewhat less clear role. Some researchers have shown the LNGFR binds and serves as a "sink" for neurotrophins.
The crystal structure of NT-3 shows that NT-3 forms a central homodimer around which two glycosylated p75 LNGFR molecules bind symmetrically. The symmetrical binding takes place along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster in the center.[15]
Cells which express both the LNGFR and the Trk receptors might therefore have a greater activity – since they have a higher "microconcentration" of the neurotrophin.
It has also been shown, however, that the LNGFR may signal a cell to die via apoptosis – so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Maisonpierre PC, Le Beau MM, Espinosa R III, Ip NY, Belluscio L, de la Monte SM, Squinto S, Furth ME, Yancopoulos GD (Oct 1991). "Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations". Genomics. 10 (3): 558–68. doi:10.1016/0888-7543(91)90436-I. PMID1889806.
^Glass DJ, Nye SH, Hantzopoulos P, Macchi MJ, Squinto SP, Goldfarb M, Yancopoulos GD (July 1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–413. doi:10.1016/0092-8674(91)90629-d. PMID1649703. S2CID43626580.
^Ip NY, Stitt TN, Tapley P, Klein R, Glass DJ, Fandl J, Greene LA, Barbacid M, Yancopoulos GD (Feb 1993). "Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells". Neuron. 10 (2): 137–149. doi:10.1016/0896-6273(93)90306-c. PMID7679912. S2CID46072027.
^Klein R, Silos-Santiago I, Smeyne R, Lira S, Brambilla R, Bryant S, Zhang L, Snider W, Barbacid M (1994). "Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements". Nature. 368 (6468): 249–51. Bibcode:1994Natur.368..249K. doi:10.1038/368249a0. PMID8145824. S2CID4328770.
^Lamballe F, Klein R, Barbacid M (1991). "trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3". Cell. 66 (5): 967–79. doi:10.1016/0092-8674(91)90442-2. PMID1653651. S2CID23448391.
^Tessarollo L, Tsoulfas P, Martin-Zanca D, Gilbert D, Jenkins N, Copeland N, Parada L (1993). "trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues". Development. 118 (2): 463–75. doi:10.1242/dev.118.2.463. PMID8223273.
^Glass DJ, Nye SH, Hantzopoulos P, Macchi MJ, Squinto SP, Goldfarb M, Yancopoulos GD (July 1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–413. doi:10.1016/0092-8674(91)90629-d. PMID1649703. S2CID43626580.
Ozçelik T, Rosenthal A, Francke U (1991). "Chromosomal mapping of brain-derived neurotrophic factor and neurotrophin-3 genes in man and mouse". Genomics. 10 (3): 569–75. doi:10.1016/0888-7543(91)90437-J. PMID1889807.
Hallböök F, Ibáñez CF, Persson H (1991). "Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary". Neuron. 6 (5): 845–58. doi:10.1016/0896-6273(91)90180-8. PMID2025430. S2CID17772282.
Ernfors P, Lee KF, Kucera J, Jaenisch R (1994). "Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents". Cell. 77 (4): 503–12. doi:10.1016/0092-8674(94)90213-5. PMID7514502. S2CID9072110.
Robinson RC, Radziejewski C, Stuart DI, Jones EY (1995). "Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer". Biochemistry. 34 (13): 4139–46. doi:10.1021/bi00013a001. PMID7703225.
Hattori M, Nanko S (1995). "Association of neurotrophin-3 gene variant with severe forms of schizophrenia". Biochem. Biophys. Res. Commun. 209 (2): 513–8. doi:10.1006/bbrc.1995.1531. PMID7733919.
Hui JO, Le J, Katta V, et al. (1996). "Human neurotrophin-3: a one-step peptide mapping method and complete disulfide characterization of the recombinant protein". J. Protein Chem. 15 (4): 351–8. doi:10.1007/BF01886861. PMID8819011. S2CID34957071.
Arinami T, Takekoshi K, Itokawa M, et al. (1996). "Failure to find associations of the CA repeat polymorphism in the first intron and the Gly-63/Glu-63 polymorphism of the neurotrophin-3 gene with schizophrenia". Psychiatr. Genet. 6 (1): 13–5. doi:10.1097/00041444-199621000-00003. PMID8925252. S2CID42610869.
Suenaga M, Ohmae H, Tsuji S, et al. (1998). "Renaturation of recombinant human neurotrophin-3 from inclusion bodies using a suppressor agent of aggregation". Biotechnol. Appl. Biochem. 28 (2): 119–24. doi:10.1111/j.1470-8744.1998.tb00521.x. PMID9756741. S2CID45466609.
Hattori M, Kunugi H, Akahane A, et al. (2002). "Novel polymorphisms in the promoter region of the neurotrophin-3 gene and their associations with schizophrenia". Am. J. Med. Genet. 114 (3): 304–9. doi:10.1002/ajmg.10248. PMID11920853.
