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Neurotrophin-3 is a protein that in humans is encoded by the NTF3 gene.^[3]^[4]

The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth 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).^[5]

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 (TrkC and TrkB - see below).

Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.^[6]^[7]

Mechanism of action

NT-3 binds three receptors on the surface of cells which are capable of responding to this growth factor:

TrkC (pronounced "Track C"), is apparently the "physiologic" receptor, in that it binds with greatest affinity to NT-3.^[8]^[9]
However, NT-3 is capable of binding and signaling through a TrkC-related receptors called TrkB.
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

TrkC is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling).

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:

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 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.^[10]

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.

References

^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ 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. PMID 1889806.
^ "Entrez Gene: NTF3 neurotrophin 3".
^ Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R, Yancopoulos G (1990). "Neurotrophin-3: a neurotrophic factor related to NGF and BDNF". Science. 247 (4949 Pt 1): 1446–51. doi:10.1126/science.2321006. PMID 2321006.
^ Tessarollo L, Vogel K, Palko M, Reid S, Parada L (1994). "Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons". Proc Natl Acad Sci USA. 91 (25): 11844–8. doi:10.1073/pnas.91.25.11844. PMC 45332 . PMID 7991545.
^ 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. doi:10.1038/368249a0. PMID 8145824.
^ 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. PMID 1653651.
^ 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. PMID 8223273.
^ Gong Y, Cao P, Yu HJ, Jiang T (August 2008). "Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex". Nature. 454 (7205): 789–93. doi:10.1038/nature07089. PMID 18596692.

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English Journal

Electrical stimulation with periodic alternating intervals stimulates neuronal cells to produce neurotrophins and cytokines through activation of mitogen-activated protein kinase pathways.

Yamamoto K1,2, Yamamoto T1, Honjo K1,2, Ichioka H1, Oseko F1, Kishida T2, Mazda O2, Kanamura N1.
European journal of oral sciences.Eur J Oral Sci.2015 Dec;123(6):403-8. doi: 10.1111/eos.12224. Epub 2015 Oct 29.
Peripheral neuropathy is a representative complication of dental surgery. Electrical therapy, based on electrical stimulation with periodic alternating intervals (ES-PAI), may promote nerve regeneration after peripheral nerve injury in a non-invasive manner, potentially providing an effective therap
PMID 26510379

Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells.

Safina DR1, Surin AM2,3,4, Pinelis VG3, Kostrov SV1,5.
Journal of neuroscience research.J Neurosci Res.2015 Dec;93(12):1865-73. doi: 10.1002/jnr.23667. Epub 2015 Sep 8.
Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are inv
PMID 26346533

Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

Duricki DA1, Hutson TH2, Kathe C3, Soleman S4, Gonzalez-Carter D2, Petruska JC5, Shine HD6, Chen Q6, Wood TC7, Bernanos M7, Cash D7, Williams SC7, Gage FH8, Moon LD9.
Brain : a journal of neurology.Brain.2015 Nov 27. pii: awv341. [Epub ahead of print]
There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h aft
PMID 26614754

Japanese Journal

Pancreatic Changes in Nerve Growth Factor/TrkA Associated with Insulin Secretion in Cerebral Ischemia

Biological and Pharmaceutical Bulletin 38(11), 1747-1751, 2015
NAID 130005106386

神経栄養因子の基礎研究とその医学的応用

YAKUGAKU ZASSHI 135(11), 1213-1226, 2015
NAID 130005105485

神経変性疾患の治療・予防薬開発を指向した神経栄養因子様活性天然物の探索研究

YAKUGAKU ZASSHI 135(10), 1147-1152, 2015
NAID 130005100625

「neurotrophin」

NTF3
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1B8K, 1BND, 1NT3, 3BUK
Identifiers
Aliases	NTF3, HDNF, NGF-2, NGF2, NT-3, NT3, neurotrophin 3
External IDs	MGI: 97380 HomoloGene: 1896 GeneCards: NTF3
Gene ontology
Molecular function	• neurotrophin p75 receptor binding; • neurotrophin receptor binding; • chemoattractant activity; • growth factor activity; • receptor binding;
Cellular component	• extracellular region; • cytoplasmic vesicle;
Biological process	• regulation of apoptotic process; • negative regulation of neuron apoptotic process; • regulation of neuron differentiation; • activation of protein kinase B activity; • neuron projection morphogenesis; • activation of GTPase activity; • positive regulation of receptor internalization; • transmembrane receptor protein tyrosine kinase signaling pathway; • positive regulation of cell migration; • cell-cell signaling; • positive regulation of peptidyl-serine phosphorylation; • induction of positive chemotaxis; • negative regulation of peptidyl-tyrosine phosphorylation; • activation of MAPK activity; • positive regulation of cell proliferation; • positive regulation of peptidyl-tyrosine phosphorylation; • positive regulation of actin cytoskeleton reorganization; • signal transduction; • positive chemotaxis; • nervous system development;
	Sources:Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	4908
	18205
	ENSG00000185652
	ENSMUSG00000049107
	P20783
	P20181
	NM_001102654; NM_002527
	NM_001164034; NM_001164035; NM_008742
	NP_001096124; NP_002518
NP_001157506.1; NP_001157507.1; NP_032768.1; NP_001157506; NP_001157507;
	NP_032768
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★] ニューロトロフィン

関: nerve growth factor、neurotrophic factor、NGF

[1] "Human PubMed Reference:".

[2] "Mouse PubMed Reference:".

[pmid1889806-3] 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. PMID 1889806.

[entrez-4] "Entrez Gene: NTF3 neurotrophin 3".

[5] Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R, Yancopoulos G (1990). "Neurotrophin-3: a neurotrophic factor related to NGF and BDNF". Science. 247 (4949 Pt 1): 1446–51. doi:10.1126/science.2321006. PMID 2321006.

[6] Tessarollo L, Vogel K, Palko M, Reid S, Parada L (1994). "Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons". Proc Natl Acad Sci USA. 91 (25): 11844–8. doi:10.1073/pnas.91.25.11844. PMC 45332 . PMID 7991545.

[7] 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. doi:10.1038/368249a0. PMID 8145824.

[8] 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. PMID 1653651.

[9] 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. PMID 8223273.

[10] Gong Y, Cao P, Yu HJ, Jiang T (August 2008). "Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex". Nature. 454 (7205): 789–93. doi:10.1038/nature07089. PMID 18596692.

v t e Cell signaling: Nervous tissue: Neurotrophic factors

Neurotrophins	NGF BDNF NT-3 NT-4

GDNF family	GDNF Artemin Neurturin Persephin

Ephrins	A1 A2 A3 A4 A5 B1 B2 B3

CNTF family	CNTF LIF IL-6

Other	GMF IGF-1 Neuregulins 1 2 3 4 PACAP VEGF

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案内

neurotrophin 3