Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1992 Mar;11(3):917–922. doi: 10.1002/j.1460-2075.1992.tb05130.x

Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor.

A Rodríguez-Tébar 1, G Dechant 1, R Götz 1, Y A Barde 1
PMCID: PMC556532  PMID: 1547788

Abstract

Neurotrophin-3 (NT-3) has low-affinity (Kd = 8 x 10(-10) M), as well as high-affinity receptors (Kd = 1.8 x 10(-11) M) on embryonic chick sensory neurons, the latter in surprisingly high numbers. Like the structurally related proteins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), NT-3 also binds to the low-affinity NGF receptor, a molecule that we suggest to designate low-affinity neurotrophin receptor (LANR). NT-3 dissociates from the LANR much more rapidly than BDNF, and more slowly than NGF. The binding of labelled NT-3 to the LANR can be reduced by half using a concentration of BDNF corresponding to the Kd of BDNF to the LANR. In contrast, the binding of NT-3 to its high-affinity neuronal receptors can only be prevented by BDNF or NGF when used at concentrations several thousand-fold higher than those corresponding to their Kd to their high-affinity neuronal receptors. Thus, specific high-affinity NT-3 receptors exist on sensory neurons that can readily discriminate between three structurally related ligands. These findings, including the remarkable property of the LANR to bind three related ligands with similar affinity, but different rate constants, are discussed.

Full text

PDF
917

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barde Y. A. The nerve growth factor family. Prog Growth Factor Res. 1990;2(4):237–248. doi: 10.1016/0955-2235(90)90021-b. [DOI] [PubMed] [Google Scholar]
  2. Bothwell M. Keeping track of neurotrophin receptors. Cell. 1991 Jun 14;65(6):915–918. doi: 10.1016/0092-8674(91)90540-f. [DOI] [PubMed] [Google Scholar]
  3. Cohen S. PURIFICATION OF A NERVE-GROWTH PROMOTING PROTEIN FROM THE MOUSE SALIVARY GLAND AND ITS NEURO-CYTOTOXIC ANTISERUM. Proc Natl Acad Sci U S A. 1960 Mar;46(3):302–311. doi: 10.1073/pnas.46.3.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cordon-Cardo C., Tapley P., Jing S. Q., Nanduri V., O'Rourke E., Lamballe F., Kovary K., Klein R., Jones K. R., Reichardt L. F. The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cell. 1991 Jul 12;66(1):173–183. doi: 10.1016/0092-8674(91)90149-s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ernfors P., Ibáez C. F., Ebendal T., Olson L., Persson H. Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454–5458. doi: 10.1073/pnas.87.14.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hallbök F., Ibáez C. F., Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991 May;6(5):845–858. doi: 10.1016/0896-6273(91)90180-8. [DOI] [PubMed] [Google Scholar]
  7. Hatanaka H., Amano T. A mouse neuroblastoma x rat glioma hybrid cell produces immunoreactive substance P-like material. Brain Res. 1981 Jun 29;215(1-2):305–316. doi: 10.1016/0006-8993(81)90509-6. [DOI] [PubMed] [Google Scholar]
  8. Herrup K., Thoenen H. Properties of the nerve growth factor receptor of a clonal line of rat pheochromocytoma (PC12) cells. Exp Cell Res. 1979 Jun;121(1):71–78. doi: 10.1016/0014-4827(79)90445-2. [DOI] [PubMed] [Google Scholar]
  9. Hofer M. M., Barde Y. A. Brain-derived neurotrophic factor prevents neuronal death in vivo. Nature. 1988 Jan 21;331(6153):261–262. doi: 10.1038/331261a0. [DOI] [PubMed] [Google Scholar]
  10. Hohn A., Leibrock J., Bailey K., Barde Y. A. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990 Mar 22;344(6264):339–341. doi: 10.1038/344339a0. [DOI] [PubMed] [Google Scholar]
  11. Jackson T. R., Hallam T. J., Downes C. P., Hanley M. R. Receptor coupled events in bradykinin action: rapid production of inositol phosphates and regulation of cytosolic free Ca2+ in a neural cell line. EMBO J. 1987 Jan;6(1):49–54. doi: 10.1002/j.1460-2075.1987.tb04717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson D., Lanahan A., Buck C. R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. doi: 10.1016/0092-8674(86)90619-7. [DOI] [PubMed] [Google Scholar]
  13. Jones K. R., Reichardt L. F. Molecular cloning of a human gene that is a member of the nerve growth factor family. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060–8064. doi: 10.1073/pnas.87.20.8060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaisho Y., Yoshimura K., Nakahama K. Cloning and expression of a cDNA encoding a novel human neurotrophic factor. FEBS Lett. 1990 Jun 18;266(1-2):187–191. doi: 10.1016/0014-5793(90)81536-w. [DOI] [PubMed] [Google Scholar]
  15. Klein R., Conway D., Parada L. F., Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell. 1990 May 18;61(4):647–656. doi: 10.1016/0092-8674(90)90476-u. [DOI] [PubMed] [Google Scholar]
  16. Klein R., Nanduri V., Jing S. A., Lamballe F., Tapley P., Bryant S., Cordon-Cardo C., Jones K. R., Reichardt L. F., Barbacid M. The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991 Jul 26;66(2):395–403. doi: 10.1016/0092-8674(91)90628-c. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knüsel B., Winslow J. W., Rosenthal A., Burton L. E., Seid D. P., Nikolics K., Hefti F. Promotion of central cholinergic and dopaminergic neuron differentiation by brain-derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):961–965. doi: 10.1073/pnas.88.3.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lamballe F., Klein R., Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991 Sep 6;66(5):967–979. doi: 10.1016/0092-8674(91)90442-2. [DOI] [PubMed] [Google Scholar]
  19. Leibrock J., Lottspeich F., Hohn A., Hofer M., Hengerer B., Masiakowski P., Thoenen H., Barde Y. A. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989 Sep 14;341(6238):149–152. doi: 10.1038/341149a0. [DOI] [PubMed] [Google Scholar]
  20. Levi-Montalcini R., Angeletti P. U. Nerve growth factor. Physiol Rev. 1968 Jul;48(3):534–569. doi: 10.1152/physrev.1968.48.3.534. [DOI] [PubMed] [Google Scholar]
  21. Maisonpierre P. C., Belluscio L., Squinto S., Ip N. Y., Furth M. E., Lindsay R. M., Yancopoulos G. D. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451. doi: 10.1126/science.247.4949.1446. [DOI] [PubMed] [Google Scholar]
  22. Middlemas D. S., Lindberg R. A., Hunter T. trkB, a neural receptor protein-tyrosine kinase: evidence for a full-length and two truncated receptors. Mol Cell Biol. 1991 Jan;11(1):143–153. doi: 10.1128/mcb.11.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Radeke M. J., Misko T. P., Hsu C., Herzenberg L. A., Shooter E. M. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature. 1987 Feb 12;325(6105):593–597. doi: 10.1038/325593a0. [DOI] [PubMed] [Google Scholar]
  24. Rodriguez-Tébar A., Barde Y. A. Binding characteristics of brain-derived neurotrophic factor to its receptors on neurons from the chick embryo. J Neurosci. 1988 Sep;8(9):3337–3342. doi: 10.1523/JNEUROSCI.08-09-03337.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rodriguez-Tébar A., Dechant G., Barde Y. A. Binding of brain-derived neurotrophic factor to the nerve growth factor receptor. Neuron. 1990 Apr;4(4):487–492. doi: 10.1016/0896-6273(90)90107-q. [DOI] [PubMed] [Google Scholar]
  26. Rohrer H., Barde Y. A. Presence and disappearance of nerve growth factor receptors on sensory neurons in culture. Dev Biol. 1982 Feb;89(2):309–315. doi: 10.1016/0012-1606(82)90320-7. [DOI] [PubMed] [Google Scholar]
  27. Rosenthal A., Goeddel D. V., Nguyen T., Lewis M., Shih A., Laramee G. R., Nikolics K., Winslow J. W. Primary structure and biological activity of a novel human neurotrophic factor. Neuron. 1990 May;4(5):767–773. doi: 10.1016/0896-6273(90)90203-r. [DOI] [PubMed] [Google Scholar]
  28. Snider W. D., Johnson E. M., Jr Neurotrophic molecules. Ann Neurol. 1989 Oct;26(4):489–506. doi: 10.1002/ana.410260402. [DOI] [PubMed] [Google Scholar]
  29. Soppet D., Escandon E., Maragos J., Middlemas D. S., Reid S. W., Blair J., Burton L. E., Stanton B. R., Kaplan D. R., Hunter T. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991 May 31;65(5):895–903. doi: 10.1016/0092-8674(91)90396-g. [DOI] [PubMed] [Google Scholar]
  30. Squinto S. P., Stitt T. N., Aldrich T. H., Davis S., Bianco S. M., Radziejewski C., Glass D. J., Masiakowski P., Furth M. E., Valenzuela D. M. trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991 May 31;65(5):885–893. doi: 10.1016/0092-8674(91)90395-F. [DOI] [PubMed] [Google Scholar]
  31. Suda K., Barde Y. A., Thoenen H. Nerve growth factor in mouse and rat serum: correlation between bioassay and radioimmunoassay determinations. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4042–4046. doi: 10.1073/pnas.75.8.4042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sutter A., Riopelle R. J., Harris-Warrick R. M., Shooter E. M. Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. J Biol Chem. 1979 Jul 10;254(13):5972–5982. [PubMed] [Google Scholar]
  33. Thoenen H., Barde Y. A. Physiology of nerve growth factor. Physiol Rev. 1980 Oct;60(4):1284–1335. doi: 10.1152/physrev.1980.60.4.1284. [DOI] [PubMed] [Google Scholar]
  34. Vale R. D., Shooter E. M. Assaying binding of nerve growth factor to cell surface receptors. Methods Enzymol. 1985;109:21–39. doi: 10.1016/0076-6879(85)09073-5. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES