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词条 Low-affinity nerve growth factor receptor
释义

  1. Neurotrophins

  2. Trk family of receptor tyrosine kinases

  3. Function

  4. Role in cancer stem cells

  5. Interactions

  6. References

  7. Further reading

  8. External links

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The low-affinity nerve growth factor receptor (nerve growth factor receptor (TNFR superfamily, member 16), also called the LNGFR or p75 neurotrophin receptor) is one of the two receptor types for the neurotrophins, a family of protein growth factors that stimulate neuronal cells to survive and differentiate. LNGFR is a member of the tumor necrosis factor receptor (TNF receptor)superfamily – indeed, LNGFR was the first member of this large family of receptors to be characterized.[1][2]

Neurotrophins

Neurotrophins include four proteins, all of which bind to the LNGFR:

nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4).

Nerve growth factor, the prototypical growth factor, is a protein secreted by a neuron's target. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high-affinity receptor tropomyosin receptor kinase A (TrkA), and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons.

The activation of TrkA by NGF is critical in inducing the survival and differentiation caused by this growth factor.

However, NGF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkA (pronounced "Track A") and the LNGFR.

Trk family of receptor tyrosine kinases

TrkA 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). There are other related Trk receptors, TrkB and TrkC. Also, there are other neurotrophic factors structurally related to NGF: BDNF (for Brain-Derived Neurotrophic Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkA mediates the effects of NGF, TrkB binds and is activated by BDNF, NT-4, and NT-3, and TrkC binds and is activated only by NT-3.

Function

Neurotrophins activating LNGFR may signal a cell to die via apoptosis, but this effect is counteracted by anti-apoptotic signaling by TrkA, TrkB, or TrkC signaling in cells that also express those receptors. LNGFR functions in a complex with Nogo receptor (NgR, Reticulon 4 receptor) to mediate RhoA-dependent inhibition of growth of regenerating axons exposed to inhibitory proteins of CNS myelin, such as Nogo, MAG or OMgP. LNGFR also activates a caspase- dependent signaling pathway that promotes developmental axon pruning, and axon degeneration in neurodegenerative disease.

Recent research has suggested a number of roles for the LNGFR, including in development of the eyes and sensory neurons,[3][4] and in repair of muscle and nerve damage in adults.[5][6][7]

Two distinct subpopulations of Olfactory ensheathing glia (being researched for nerve repair) have been identified[8] with high or low cell surface expression of low-affinity nerve growth factor receptor (p75).

Role in cancer stem cells

LNGFR has been implicated as a marker for cancer stem cells in melanoma and other cancers. Melanoma cells transplanted into an immunodeficient mouse model were shown to require expression of CD271 in order to grow a melanoma.[9] Gene knockdown of CD271 has also been shown to abolish neural crest stem cell properties of melanoma cells and decrease genomic stability leading to a reduced migration, tumorigenicity, proliferation and induction of apoptosis.[10][11][12] Furthermore, increased levels of CD271 were observed in brain metastatic melanoma cells whereas resistance to the BRAF inhibitor vemurafenib supposedly selects for highly malignant brain and lung-metastasizing melanoma cells.[13][14][15][16]

Interactions

Low-affinity nerve growth factor receptor has been shown to interact with:

{{div col|colwidth=20em}}
  • FSCN1,[17]
  • MAGEH1,[18]
  • NDN,[18][19][20]
  • NGFRAP1[21]
  • NGF,[22][23]
  • PRKACB,[24]
  • TRAF2,[26] and
  • TRAF4.[25][26]
{{Div col end}}

References

1. ^{{cite journal | vauthors = Johnson D, Lanahan A, Buck CR, Sehgal A, Morgan C, Mercer E, Bothwell M, Chao M | title = Expression and structure of the human NGF receptor | journal = Cell | volume = 47 | issue = 4 | pages = 545–54 | date = November 1986 | pmid = 3022937 | doi = 10.1016/0092-8674(86)90619-7 }}
2. ^{{cite journal | vauthors = Radeke MJ, Misko TP, Hsu C, Herzenberg LA, Shooter EM | title = Gene transfer and molecular cloning of the rat nerve growth factor receptor | journal = Nature | volume = 325 | issue = 6105 | pages = 593–7 | year = 1987 | pmid = 3027580 | doi = 10.1038/325593a0 }}
3. ^{{cite journal | vauthors = Nicol GD | title = Nerve growth factor, sphingomyelins, and sensitization in sensory neurons | journal = Sheng Li Xue Bao | volume = 60 | issue = 5 | pages = 603–4 | date = October 2008 | pmid = 18958367 | doi = }}
4. ^{{cite journal | vauthors = Di Girolamo N, Sarris M, Chui J, Cheema H, Coroneo MT, Wakefield D | title = Localization of the low-affinity nerve growth factor receptor p75 in human limbal epithelial cells | journal = Journal of Cellular and Molecular Medicine | volume = 12 | issue = 6B | pages = 2799–811 | date = December 2008 | pmid = 19210757 | pmc = 3828893 | doi = 10.1111/j.1582-4934.2008.00290.x }}
5. ^{{cite journal | vauthors = Chen LW, Yung KK, Chan YS, Shum DK, Bolam JP | title = The proNGF-p75NTR-sortilin signalling complex as new target for the therapeutic treatment of Parkinson's disease | journal = CNS & Neurological Disorders Drug Targets | volume = 7 | issue = 6 | pages = 512–23 | date = December 2008 | pmid = 19128208 | doi = 10.2174/187152708787122923 }}
6. ^{{cite journal | vauthors = Kocsis JD, Lankford KL, Sasaki M, Radtke C | title = Unique in vivo properties of olfactory ensheathing cells that may contribute to neural repair and protection following spinal cord injury | journal = Neuroscience Letters | volume = 456 | issue = 3 | pages = 137–42 | date = June 2009 | pmid = 19429149 | pmc = 2713444 | doi = 10.1016/j.neulet.2008.08.093 }}
7. ^{{cite journal | vauthors = Deponti D, Buono R, Catanzaro G, De Palma C, Longhi R, Meneveri R, Bresolin N, Bassi MT, Cossu G, Clementi E, Brunelli S | title = The low-affinity receptor for neurotrophins p75NTR plays a key role for satellite cell function in muscle repair acting via RhoA | journal = Molecular Biology of the Cell | volume = 20 | issue = 16 | pages = 3620–7 | date = August 2009 | pmid = 19553472 | pmc = 2777922 | doi = 10.1091/mbc.E09-01-0012 }}
8. ^{{cite journal | vauthors = Honoré A, Le Corre S, Derambure C, Normand R, Duclos C, Boyer O, Marie JP, Guérout N | title = Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the olfactory bulb | journal = Glia | volume = 60 | issue = 3 | pages = 404–13 | date = March 2012 | pmid = 22161947 | doi = 10.1002/glia.22274 }}
9. ^{{cite journal | vauthors = Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, Butler PD, Yang GP, Joshua B, Kaplan MJ, Longaker MT, Weissman IL | title = Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 | journal = Nature | volume = 466 | issue = 7302 | pages = 133–7 | date = July 2010 | pmid = 20596026 | pmc = 2898751 | doi = 10.1038/nature09161 }}
10. ^{{cite journal | vauthors = Redmer T, Welte Y, Behrens D, Fichtner I, Przybilla D, Wruck W, Yaspo ML, Lehrach H, Schäfer R, Regenbrecht CR | title = The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells | journal = PLOS One | volume = 9 | issue = 5 | pages = e92596 | year = 2014 | pmid = 24799129 | pmc = 4010406 | doi = 10.1371/journal.pone.0092596 }}
11. ^{{cite journal | vauthors = Redmer T, Walz I, Klinger B, Khouja S, Welte Y, Schäfer R, Regenbrecht C | title = The role of the cancer stem cell marker CD271 in DNA damage response and drug resistance of melanoma cells | journal = Oncogenesis | volume = 6 | issue = 1 | pages = e291 | date = January 2017 | pmid = 28112719 | pmc = 5294251 | doi = 10.1038/oncsis.2016.88 }}
12. ^{{cite journal | vauthors = Radke J, Roßner F, Redmer T | title = CD271 determines migratory properties of melanoma cells | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 9834 | date = August 2017 | pmid = 28852061 | pmc = 5574914 | doi = 10.1038/s41598-017-10129-z }}
13. ^{{cite journal | vauthors = Guo R, Fierro-Fine A, Goddard L, Russell M, Chen J, Liu CZ, Fung KM, Hassell LA | title = Increased expression of melanoma stem cell marker CD271 in metastatic melanoma to the brain | journal = International Journal of Clinical and Experimental Pathology | volume = 7 | issue = 12 | pages = 8947–51 | date = 2014 | pmid = 25674270 | pmc = 4313973 }}
14. ^{{cite journal | vauthors = Radke J, Roßner F, Redmer T | title = CD271 determines migratory properties of melanoma cells | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 9834 | date = August 2017 | pmid = 28852061 | doi = 10.1038/s41598-017-10129-z }}
15. ^{{cite journal | vauthors = Zubrilov I, Sagi-Assif O, Izraely S, Meshel T, Ben-Menahem S, Ginat R, Pasmanik-Chor M, Nahmias C, Couraud PO, Hoon DS, Witz IP | title = Vemurafenib resistance selects for highly malignant brain and lung-metastasizing melanoma cells | journal = Cancer Letters | volume = 361 | issue = 1 | pages = 86–96 | date = May 2015 | pmid = 25725450 | doi = 10.1016/j.canlet.2015.02.041 }}
16. ^{{cite journal | vauthors = Redmer T | title = Deciphering mechanisms of brain metastasis in melanoma - the gist of the matter | language = En | journal = Molecular Cancer | volume = 17 | issue = 1 | pages = 106 | date = July 2018 | pmid = 30053879 | pmc = 6064184 | doi = 10.1186/s12943-018-0854-5 }}
17. ^{{cite journal | vauthors = Shonukan O, Bagayogo I, McCrea P, Chao M, Hempstead B | title = Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin | journal = Oncogene | volume = 22 | issue = 23 | pages = 3616–23 | date = June 2003 | pmid = 12789270 | doi = 10.1038/sj.onc.1206561 }}
18. ^1 {{cite journal | vauthors = Tcherpakov M, Bronfman FC, Conticello SG, Vaskovsky A, Levy Z, Niinobe M, Yoshikawa K, Arenas E, Fainzilber M | title = The p75 neurotrophin receptor interacts with multiple MAGE proteins | journal = The Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49101–4 | date = December 2002 | pmid = 12414813 | doi = 10.1074/jbc.C200533200 }}
19. ^{{cite journal | vauthors = Kuwako K, Taniura H, Yoshikawa K | title = Necdin-related MAGE proteins differentially interact with the E2F1 transcription factor and the p75 neurotrophin receptor | journal = The Journal of Biological Chemistry | volume = 279 | issue = 3 | pages = 1703–12 | date = January 2004 | pmid = 14593116 | doi = 10.1074/jbc.M308454200 }}
20. ^{{cite journal | vauthors = Bronfman FC, Tcherpakov M, Jovin TM, Fainzilber M | title = Ligand-induced internalization of the p75 neurotrophin receptor: a slow route to the signaling endosome | journal = The Journal of Neuroscience | volume = 23 | issue = 8 | pages = 3209–20 | date = April 2003 | pmid = 12716928 | doi = 10.1523/JNEUROSCI.23-08-03209.2003}}
21. ^{{cite journal | vauthors = Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA | title = NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR | journal = The Journal of Biological Chemistry | volume = 275 | issue = 23 | pages = 17566–70 | date = June 2000 | pmid = 10764727 | doi = 10.1074/jbc.C000140200 }}
22. ^{{cite journal | vauthors = Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM | title = Sortilin is essential for proNGF-induced neuronal cell death | journal = Nature | volume = 427 | issue = 6977 | pages = 843–8 | date = February 2004 | pmid = 14985763 | doi = 10.1038/nature02319 }}
23. ^{{cite journal | vauthors = Lee R, Kermani P, Teng KK, Hempstead BL | title = Regulation of cell survival by secreted proneurotrophins | journal = Science | volume = 294 | issue = 5548 | pages = 1945–8 | date = November 2001 | pmid = 11729324 | doi = 10.1126/science.1065057 }}
24. ^{{cite journal | vauthors = Higuchi H, Yamashita T, Yoshikawa H, Tohyama M | title = PKA phosphorylates the p75 receptor and regulates its localization to lipid rafts | journal = The EMBO Journal | volume = 22 | issue = 8 | pages = 1790–800 | date = April 2003 | pmid = 12682012 | pmc = 154469 | doi = 10.1093/emboj/cdg177 }}
25. ^1 {{cite journal | vauthors = Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE | title = TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction | journal = The Journal of Biological Chemistry | volume = 274 | issue = 42 | pages = 30202–8 | date = October 1999 | pmid = 10514511 | doi = 10.1074/jbc.274.42.30202 }}
26. ^{{cite journal | vauthors = Krajewska M, Krajewski S, Zapata JM, Van Arsdale T, Gascoyne RD, Berern K, McFadden D, Shabaik A, Hugh J, Reynolds A, Clevenger CV, Reed JC | title = TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues | journal = The American Journal of Pathology | volume = 152 | issue = 6 | pages = 1549–61 | date = June 1998 | pmid = 9626059 | pmc = 1858434 | doi = }}

Further reading

{{Refbegin | 2}}
  • {{cite journal | vauthors = Buxser S, Puma P, Johnson GL | title = Properties of the nerve growth factor receptor. Relationship between receptor structure and affinity | journal = The Journal of Biological Chemistry | volume = 260 | issue = 3 | pages = 1917–26 | date = February 1985 | pmid = 2981877 | url = http://www.jbc.org/cgi/content/abstract/260/3/1917 }}
  • {{cite journal | vauthors = Glass DJ, Nye SH, Hantzopoulos P, Macchi MJ, Squinto SP, Goldfarb M, Yancopoulos GD | title = TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor | journal = Cell | volume = 66 | issue = 2 | pages = 405–13 | date = July 1991 | pmid = 1649703 | doi = 10.1016/0092-8674(91)90629-D }}
  • {{cite journal | vauthors = Ibáñez CF | title = Jekyll-Hyde neurotrophins: the story of proNGF | journal = Trends in Neurosciences | volume = 25 | issue = 6 | pages = 284–6 | date = June 2002 | pmid = 12086739 | doi = 10.1016/S0166-2236(02)02169-0 }}
  • {{cite journal | vauthors = Radeke MJ, Misko TP, Hsu C, Herzenberg LA, Shooter EM | title = Gene transfer and molecular cloning of the rat nerve growth factor receptor | journal = Nature | volume = 325 | issue = 6105 | pages = 593–7 | year = 1987 | pmid = 3027580 | doi = 10.1038/325593a0 }}
{{Refend}}

External links

  • {{MeshName|Nerve+Growth+Factor+Receptor,+Low-Affinity}}
{{PDB Gallery|geneid=4804}}{{Growth factor receptors}}{{Clusters of differentiation}}{{Tumor necrosis factor receptor superfamily}}{{Growth factor receptor modulators}}{{DEFAULTSORT:Low-Affinity Nerve Growth Factor Receptor}}

3 : Clusters of differentiation|TNF receptor family|Neurochemistry
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