Neurotrophin-3 is aprotein that in humans is encoded by theNTF3gene.[5][6]
Theprotein encoded by this gene, NT-3, is aneurotrophic factor in the NGF (Nerve Growth Factor) family ofneurotrophins. It is aproteingrowth factor which has activity on certainneurons of the peripheral andcentral nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons andsynapses. NT-3 was the third neurotrophic factor to be characterized, afternerve growth factor (NGF) andBDNF (Brain Derived Neurotrophic Factor).[7]
Although the vast majority of neurons in themammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neuralstem cells; a process known asneurogenesis. 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 andTrkB).[8][9]
As mentioned above, there are other related Trk receptors,TrkA andTrkB. Also as mentioned, there are other neurotrophic factors structurally related to NT-3:
The other NT-3 receptor, theLNGFR, 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 centralhomodimer around which twoglycosylated 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 viaapoptosis – so therefore cells expressing the LNGFR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.
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^"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.
^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.
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