Neurotrophin-3
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| Location (UCSC) | Chr 12: 5.43 – 5.52 Mb | Chr 6: 126.08 – 126.14 Mb | |||||||
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Neurotrophin-3 is a protein that in humans is encoded by the NTF3 gene.[5][6]
The
BDNF (Brain Derived Neurotrophic Factor).[7]
Function
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 (
Mice born without the ability to make NT-3 have loss of
Mechanism of action
NT-3 binds three receptors on the surface of cells which are capable of responding to this growth factor:
- However, NT-3 is capable of binding and signaling through a TrkC-related receptors called TrkB.[14]
- Finally, NT-3 also binds a second-receptor type besides Trk receptors, called the LNGFR(for "low affinity nerve growth factor receptor).
High affinity receptors
cellular signaling
).
As mentioned above, there are other related Trk receptors,
TrkB
. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
- NGF (for "Nerve Growth Factor")
- BDNF(for "Brain Derived Neurotrophic Factor")
- NT-4(for "Neurotrophin-4")
While TrkB mediates the effects of BDNF, NT-4, and NT-3,
TrkA binds and is activated by NGF
, and TrkC binds and is activated only by NT-3.
Low affinity receptors
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
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.
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000185652 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049107 – Ensembl, May 2017
- ^ "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.
- PMID 1889806.
- ^ "Entrez Gene: NTF3 neurotrophin 3".
- S2CID 37763746.
- S2CID 43626580.
- S2CID 46072027.
- PMID 7991545.
- S2CID 4328770.
- S2CID 23448391.
- PMID 8223273.
- S2CID 43626580.
- S2CID 4333271.
Further reading
- Kalcheim C, Carmeli C, Rosenthal A (1992). "Neurotrophin 3 is a mitogen for cultured neural crest cells". Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1661–5. PMID 1542658.
- 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. PMID 1889807.
- 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. S2CID 17772282.
- Jones KR, Reichardt LF (1990). "Molecular cloning of a human gene that is a member of the nerve growth factor family". Proc. Natl. Acad. Sci. U.S.A. 87 (20): 8060–4. PMID 2236018.
- Rosenthal A, Goeddel DV, Nguyen T, et al. (1990). "Primary structure and biological activity of a novel human neurotrophic factor". Neuron. 4 (5): 767–73. S2CID 30148948.
- Kaisho Y, Yoshimura K, Nakahama K (1990). "Cloning and expression of a cDNA encoding a novel human neurotrophic factor". FEBS Lett. 266 (1–2): 187–91. S2CID 7645464.
- 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. S2CID 9072110.
- Robinson RC, Radziejewski C, Stuart DI, Jones EY (1995). "Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer". Biochemistry. 34 (13): 4139–46. PMID 7703225.
- Hattori M, Nanko S (1995). "Association of neurotrophin-3 gene variant with severe forms of schizophrenia". Biochem. Biophys. Res. Commun. 209 (2): 513–8. PMID 7733919.
- Tessarollo L, Vogel KS, Palko ME, et al. (1995). "Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons". Proc. Natl. Acad. Sci. U.S.A. 91 (25): 11844–8. PMID 7991545.
- Rydén M, Ibáñez CF (1996). "Binding of neurotrophin-3 to p75LNGFR, TrkA, and TrkB mediated by a single functional epitope distinct from that recognized by trkC". J. Biol. Chem. 271 (10): 5623–7. PMID 8621424.
- 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. S2CID 34957071.
- Donovan MJ, Hahn R, Tessarollo L, Hempstead BL (1996). "Identification of an essential nonneuronal function of neurotrophin 3 in mammalian cardiac development". Nat. Genet. 14 (2): 210–3. S2CID 9259115.
- 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. S2CID 42610869.
- Urfer R, Tsoulfas P, O'Connell L, et al. (1998). "High resolution mapping of the binding site of TrkA for nerve growth factor and TrkC for neurotrophin-3 on the second immunoglobulin-like domain of the Trk receptors". J. Biol. Chem. 273 (10): 5829–40. PMID 9488719.
- 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. S2CID 45466609.
- Hochhaus F, Koehne P, Schäper C, et al. (2003). "Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus". BMC Pediatrics. 1: 2. PMID 11580868.
- Kobayashi H, Gleich GJ, Butterfield JH, Kita H (2002). "Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli". Blood. 99 (6): 2214–20. PMID 11877300.
- 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. PMID 11920853.
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