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Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth

Nature Neuroscience volume 3, pages 342–349 (2000)Cite this article

Abstract

Neurotrophin regulation of neuronal morphology is complex and may involve differential action of alternative Trk receptor isoforms. We transfected ferret visual cortical slices with full-length and truncated TrkB receptors to examine their roles in regulating cortical dendrite development. These TrkB isoforms had differential effects on dendritic arborization: whereas full-length TrkB increased proximal dendritic branching, truncated TrkB promoted net elongation of distal dendrites. The morphological effects of each receptor isoform were distinct, yet their actions inhibited one another. Actions of the truncated TrkB receptor did not involve unmasking of endogenous TrkC signaling. These results suggest that TrkB receptors do not regulate dendritic growth per se but, rather, the mode of such growth.

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Figure 1: Cotransfection of TrkB isoforms and BFP into cortical pyramidal neurons using particle-mediated gene transfer.
Figure 2: Layer VI pyramidal neurons transfected with epitope-tagged TrkB isoforms.
Figure 3: T1 and full-length TrkB transfections induce outgrowth in distinct regions of the dendritic arbor.
Figure 4: Full-length TrkB increases dendritic branching whereas T1 induces elongation of pre-existing dendrites.
Figure 5: BDNF and NT-4/5 potentiate full-length TrkB's dendritic effects but not those of T1.
Figure 6: K252a blocks proximal dendritic outgrowth induced by exogenous and endogenous full-length TrkB receptor activation.
Figure 7: T1 induces distal dendritic growth by inhibiting full-length TrkB activation.
Figure 8: T1's effects on morphology are not mediated by TrkC.

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References

  1. Bonhoeffer, T. Neurotrophins and activity-dependent development of the neocortex. Curr. Opin. Neurobiol. 6, 119–126 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Cellerino, A. & Maffei, L. The action of neurotrophins in the development and plasticity of the visual cortex. Prog. Neurobiol. 49, 53–71 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Lewin, G. R. & Barde, Y. A. Physiology of the neurotrophins. Annu. Rev. Neurosci. 19, 289–317 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. McAllister, A. K., Katz, L. C. & Lo, D. C. Neurotrophins and synaptic plasticity. Annu. Rev. Neurosci. 22, 295–318 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Purves, D., Snider, W. D. & Voyvodic, J. T. Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system. Nature 336, 123–128 (1988).

    Article  CAS  PubMed  Google Scholar 

  6. Snider, W. D. Nerve growth factor enhances dendritic arborization of sympathetic ganglion cells in developing mammals. J. Neurosci. 8, 2628–2634 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shimada, A., Mason, C. A. & Morrison, M. E. TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells. J. Neurosci. 18, 8559–8570 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lentz, S. I., Knudson, C. M., Korsmeyer, S. J. & Snider, W. D. Neurotrophins support the development of diverse sensory axon morphologies. J. Neurosci. 19, 1038–1048 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lom, B. & Cohen-Cory, S. Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo. J. Neurosci. 19, 9928–9938 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. McAllister, A. K., Lo, D. C. & Katz, L. C. Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 15, 791–803 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. McAllister, A. K., Katz, L. C. & Lo, D. C. Opposing roles for endogenous BDNF and NT-3 in regulating cortical dendritic growth. Neuron 18, 767–778 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Maffei, L., Berardi, N., Domenici, L., Parisi, V. & Pizzorusso, T. Nerve growth factor (NGF) prevents the shift in ocular dominance distribution of visual cortical neurons in monocularly deprived rats. J. Neurosci. 12, 4651–4662 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Galuske, R. A., Kim, D. S., Castren, E., Thoenen, H. & Singer, W. Brain-derived neurotrophic factor reversed experience-dependent synaptic modifications in kitten visual cortex. Eur. J. Neurosci. 8, 1554–1559 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Cabelli, R. J., Shelton, D. L., Segal, R. A. & Shatz, C. J. Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns. Neuron 19, 63–76 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Barbacid, M. The Trk family of neurotrophin receptors. J. Neurobiol. 25, 1386–1403 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Lamballe, F., Tapley, P. & Barbacid, M. trkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. EMBO J. 12, 3083–3094 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Valenzuela, D. M. et al. Alternative forms of rat TrkC with different functional capabilities. Neuron 10, 963–974 (1993).

    Article  CAS  PubMed  Google Scholar 

  18. Strohmaier, C., Carter, B. D., Urfer, R., Barde, Y. A. & Dechant, G. A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor. EMBO J. 15, 3332–3337 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Holtzman, D. M. et al. p140trk mRNA marks NGF-responsive forebrain neurons: evidence that trk gene expression is induced by NGF. Neuron 9, 465–478 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Knusel, B., Rabin, S. J., Hefti, F. & Kaplan, D. R. Regulated neurotrophin receptor responsiveness during neuronal migration and early differentiation. J. Neurosci. 14, 1542–1554 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Frisen, J. et al. Characterization of glial trkB receptors: differential response to injury in the central and peripheral nervous systems. Proc. Natl. Acad. Sci. USA 90, 4971–4975 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rudge, J. S. et al. Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes. Eur. J. Neurosci. 6, 693–705 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Armanini, M. P., McMahon, S. B., Sutherland, J., Shelton, D. L. & Phillips, H. S. Truncated and catalytic isoforms of trkB are co-expressed in neurons of rat and mouse CNS. Eur. J. Neurosci. 7, 1403–1409 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Biffo, S., Offenhauser, N., Carter, B. D. & Barde, Y. A. Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development. Development 121, 2461–2470 (1995).

    CAS  PubMed  Google Scholar 

  25. Wetmore, C. & Olson, L. Neuronal and nonneuronal expression of neurotrophins and their receptors in sensory and sympathetic ganglia suggest new intercellular trophic interactions. J. Comp. Neurol. 353, 143–159 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Escandon, E. et al. Regulation of neurotrophin receptor expression during embryonic and postnatal development. J. Neurosci. 14, 2054–2068 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Allendoerfer, K. L. et al. Regulation of neurotrophin receptors during the maturation of the mammalian visual system. J. Neurosci. 14, 1795–1811 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fryer, R. H. et al. Developmental and mature expression of full-length and truncated TrkB receptors in the rat forebrain. J. Comp. Neurol. 374, 21–40 (1996).

    Article  CAS  PubMed  Google Scholar 

  29. Eide, F. F. et al. Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling. J. Neurosci. 16, 3123–3129 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ninkina, N. et al. Expression and function of TrkB variants in developing sensory neurons. EMBO J. 15, 6385–6393 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fryer, R. H., Kaplan, D. R. & Kromer, L. F. Truncated trkB receptors on nonneuronal cells inhibit BDNF-induced neurite outgrowth in vitro. Exp. Neurol. 148, 616–627 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Baxter, G. T. et al. Signal transduction mediated by the truncated trkB receptor isoforms, trkB.T1 and trkB.T2. J. Neurosci. 17, 2683–2690 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Arnold, D., Feng, L., Kim, J. & Heintz, N. A strategy for the analysis of gene expression during neural development. Proc. Natl. Acad. Sci. USA 91, 9970–9974 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lo, D. C., McAllister, A. K. & Katz, L. C. Neuronal transfection in brain slices using particle-mediated gene transfer. Neuron 13, 1263–1268 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Jackson, C. A., Peduzzi, J. D. & Hickey, T. L. Visual cortex development in the ferret. I. Genesis and migration of visual cortical neurons. J. Neurosci. 9, 1242–1253 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zervas, M. & Walkley, S. U. Ferret pyramidal cell dendritogenesis: changes in morphology and ganglioside expression during cortical development. J. Comp. Neurol. 413, 429–448 (1999).

    Article  CAS  PubMed  Google Scholar 

  37. Haapasalo, A. et al. Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells. Oncogene 18, 1285–1296 (1999).

    Article  CAS  PubMed  Google Scholar 

  38. Kryl, D. et al. Subcellular localization of full-length and truncated Trk receptor isoforms in polarized neurons and epithelial cells. J. Neurosci. 19, 5823–5833 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W. & Prasher, D. C. Green fluorescent protein as a marker for gene expression. Science 263, 802–805 (1994).

    Article  CAS  PubMed  Google Scholar 

  40. Sholl, D. Dendritic organization in the neurons of the visual and motor cortices of the cat. J. Anat. 87, 387–406 (1953).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Berg, M. M., Sternberg, D. W., Parada, L. F. & Chao, M. V. K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J. Biol. Chem. 267, 13–16 (1992).

    CAS  PubMed  Google Scholar 

  42. Tapley, P., Lamballe, F. & Barbacid, M. K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors. Oncogene 7, 371–381 (1992).

    CAS  PubMed  Google Scholar 

  43. Wu, G. Y., Zou, D. J., Rajan, I. & Cline, H. Dendritic dynamics in vivo change during neuronal maturation. J. Neurosci. 19, 4472–4483 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ninkina, N., Grashchuck, M., Buchman, V. L. & Davies, A. M. TrkB variants with deletions in the leucine-rich motifs of the extracellular domain. J. Biol. Chem. 272, 13019–13025 (1997).

    Article  CAS  PubMed  Google Scholar 

  45. Garner, A. S. et al. Expression of TrkB receptor isoforms in the developing avian visual system. J. Neurosci. 16, 1740–1752 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Boeshore, K. L., Luckey, C. N., Zigmond, R. E. & Large, T. H. TrkB isoforms with distinct neurotrophin specificities are expressed in predominantly nonoverlapping populations of avian dorsal root ganglion neurons. J. Neurosci. 19, 4739–4747 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tsoulfas, P., Stephens, R. M., Kaplan, D. R. & Parada, L. F. TrkC isoforms with inserts in the kinase domain show impaired signaling responses. J. Biol. Chem. 271, 5691–5697 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Dechant, G. & Barde, Y. A. Signalling through the neurotrophin receptor p75NTR. Curr. Opin. Neurobiol. 7, 413–418 (1997).

    Article  CAS  PubMed  Google Scholar 

  49. Barker, P. A. p75NTR: a study in contrasts. Cell Death Differ. 5, 346–356 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Kang, H. & Schuman, E. M. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267, 1658–1662 (1995).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank D. Kryl and P. Barker for providing myc-tagged TrkB and TrkC plasmids, A. Haapasalo and E. Castren for providing FLAG-tagged TrkB, M. Bolton, N. Cant, D. Chikaraishi, L. Katz, J. McNamara, A. Pittman and N. Tang Sherwood for comments and advice and Regeneron Pharmaceuticals for providing BDNF and NT-4/5. This work was supported by grants from the NIH (NEI EY11553), the McKnight Endowment Fund for Neuroscience, the Ruth K. Broad Biomedical Research Foundation and the Duke Medical Scientist Training Program.

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  1. Department of Neurobiology, Duke University Medical Center, Box 3209, Durham, 27710, North Carolina, USA

    Talene A. Yacoubian & Donald C. Lo

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Correspondence to Donald C. Lo.

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Yacoubian, T., Lo, D. Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth. Nat Neurosci 3, 342–349 (2000). https://doi.org/10.1038/73911

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