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14-September-2008 18:02:48 - Neurotrophin-3 Neurotrophin 3 PDB rendering based on 1b8k. Available structures: 1b8k, 1bnd, 1nt3 Identifiers Symbols NTF3; NT3; HDNF; MGC129711; NGF-2; NGF2 External IDs OMIM: 162660 MGI: 97380 HomoloGene: 1896 Gene ontology Molecular function: growth factor activity Cellular component: cytoplasmic membrane-bound vesicle Biological process: anti-apoptosis cell motility signal transduction cell-cell signaling neuromuscular synaptic transmission glial cell fate determination axon guidance brain development peripheral nervous system development epidermis development nerve development mechanoreceptor differentiation regulation of neuron apoptosis positive regulation of transcription from RNA polymerase II promoter enteric nervous system development generation of neurons smooth muscle cell differentiation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 4908 18205 Ensembl ENSG00000185652 ENSMUSG00000049107 Uniprot P20783 Q3V1A4 Refseq NM_002527 mRNA NP_002518 protein NM_008742 mRNA NP_032768 protein Location Chr 12: 5.47 - 5.47 Mb Chr 6: 126.07 - 126.13 Mb Pubmed search 1 2 Neurotrophin 3, also known as NTF3, is a human gene.1 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 Neurotrohic Factor.2 Contents 1 Function 2 Mechanism of action 2.1 High affinity receptors 2.2 Low affinity receptors 3 References 4 Further reading 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.34 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-3.56 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. 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 ^ 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 U S A 91 25: 11844-8. doi:10.1073/pnas.91.25.11844. 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:10.1016/0092-86749190442-2. 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. 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. Maisonpierre PC, Le Beau MM, Espinosa R, et al. 1991. Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations.. Genomics 10 3: 558-68. PMID 1889806. 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. PMID 2025430. 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. PMID 2344409. 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. PMID 2365067. 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. PMID 7514502. 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. doi:10.1006/bbrc.1995.1531. 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. PMID 8819011. 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. doi:10.1038/ng1096-210. PMID 8841198. 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. PMID 8925252. 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 Pt 2: 119-24. PMID 9756741. 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. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Cell signaling: nervous tissue: neurotrophin Trk binding NGF - BDNF - NT-3 - NT-4 GFL GDNF - Neurturin - Artemin - Persephin Other CNTF - GMF - Neuregulin Neuregulin 1 - PACAP Retrieved from http://en..org/wiki/Neurotrophin-3 Categories: Genes on chromosome 12 | Human proteins | Cell signaling | Signal transduction | Neurotrophins | Peptide hormones | Growth factors | Developmental neuroscience | Proteins Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Nederlands This page was last modified on 8 July 2008, at 02:42
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