Skip to main content

Advertisement

Log in

The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The cellular prion protein (PrPC) is found prominently at the synapse. However, its role at the nerve termini and elsewhere is unknown. Here we discuss research presented at the 2005 International Institute for Complex Adaptive Matter (I2CAM) first Annual Amyloid Conference that provides insight into the role of synaptic PrPC. The prion protein can interact and facilitate copper uptake at the synapse, is presumed to oligodimerize to facilitate putative cell-cell adhesion, and it transports toward the synapse by fast microtubule-based anterograde transport. While PrPC appears to be involved in all these processes, the mechanisms of PrPC function in each of them remain unclear. A role for PrPC in these distinct processes suggests a complex role for this protein at the synapse. Unraveling PrPC function will likely entail employing combined approaches that take into account its possible multifaceted functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aplin, A. E., Howe, A., Alahari, S. K., & Juliano, R. L. (1998). Signal transduction and signal modulation by cell adhesion receptors: The role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins. Pharmacological Reviews, 50, 197–263.

    PubMed  CAS  Google Scholar 

  • Bailly, Y., Haeberle, A. M., Blanquet-Grossard, F., Chasserot-Golaz, S., Grant, N., Schulze, T., et al. (2004). Prion protein (PrPC) immunocytochemistry and expression of the green fluorescent protein reporter gene under control of the bovine PrP gene promoter in the mouse brain. Journal of Comparative Neurology, 473, 244–269.

    Article  PubMed  CAS  Google Scholar 

  • Baldwin, M. A. (2005). Analysis of glycosylphosphatidylinositol protein anchors: The prion protein. Methods in Enzymology, 405, 172–187.

    Article  PubMed  CAS  Google Scholar 

  • Baloui, H., von Boxberg, Y., Vinh, J., Weiss, S., Rossier, J., Nothias, F., et al. (2004). Cellular prion protein/laminin receptor: Distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neurons. European Journal of Neuroscience, 20, 2605–2616.

    Article  PubMed  Google Scholar 

  • Bendheim, P. E., Brown, H. R., Rudelli, R. D., Scala, L. J., Goller, N. L., Wen, G. Y., et al. (1992). Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology, 42, 149–156.

    PubMed  CAS  Google Scholar 

  • Brown, D. R. (1999). Prion protein expression aids cellular uptake and veratridine-induced release of copper. Journal of Neuroscience Research, 58, 712–717

    Article  Google Scholar 

  • Brown, D. R., Qin, K., Herms, J. W., Madlung, A., Manson, J., Strome, R., et al. (1997). The cellular prion protein binds copper in vivo. Nature, 390, 684–687.

    Article  PubMed  CAS  Google Scholar 

  • Buckley, C. D., Rainger, G. E., Brad¢eld, P. F., Nash, G. B., & Simmons, D. L. (1998). Cell adhesion: More than just glue. Molecular Membrane Biology, 15, 167–176.

    PubMed  CAS  Google Scholar 

  • Chishti, M. A., Strome, R., Carlson, G. A., & Westaway, D. (1997). Syrian hamster prion protein (PrP(C)) is expressed in photoreceptor cells of the adult retina. Neuroscience Letters, 234, 11–14.

    Article  PubMed  CAS  Google Scholar 

  • Collinge, J., Whittington, M. A., Sidle, K. C., Smith, C. J., Palmer, M. S., Clarke, A. R., et al. (1994). Prion protein is necessary for normal synaptic function. Nature, 370, 295–297.

    Article  PubMed  CAS  Google Scholar 

  • DeArmond, S. J., Mobley, W. C., DeMott, D. L., Barry, R. A., Beckstead, J. H., & Prusiner, S. B. (1987). Changes in the localization of brain prion proteins during scrapie infection. Neurology, 37, 1271–1280.

    PubMed  CAS  Google Scholar 

  • Ford, M. J., Burton, K. J., Morris, R. J., & Hall, S. M. (2002). Selective expression of prion protein in peripheral tissues of the adult mouse. Neuroscience, 113, 177–192.

    Article  PubMed  CAS  Google Scholar 

  • Fournier, J.-G., Escaig-Haye, F., Billette de Villemeur, T., & Robain, O. (1995). Ultrastructural localization of cellular prion protein (PrPC) in synaptic boutons of normal hamster hippocampus. Comptes Rendus de l'AcadeÂmie des Sciences. Paris, III 318, 339–344.

    Google Scholar 

  • Gabizon, R., Meiner, Z., Halimi, M., & Ben-Sasson, S. A. (1993). Heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate. Journal of Cellular Physiology, 157, 319–325.

    Article  PubMed  CAS  Google Scholar 

  • Gauczynski, S., Peyrin, J. M., Haik, S., Leucht, C., Hundt, C., Rieger, R., et al. (2001). The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO Journal, 20, 5863–5875.

    Article  PubMed  CAS  Google Scholar 

  • Guzik, B. W., & Goldstein, L. S. (2004). Microtubule-dependent transport in neurons: Steps towards an understanding of regulation, function and dysfunction. Current Opinion in Cell Biology, 16, 443–450.

    Article  PubMed  CAS  Google Scholar 

  • Harris, D. A., Peters, P. J., Taraboulos, A., Lingappa, V., DeArmond, S. J., & Prusiner, S. B. (2003). Cell biology of prions. In S. B. Prusiner (Ed.), Prion biology and diseases (2nd ed., pp. 483–544).

  • Herms, J., Tings, T., Gall, S., Madlung, A., Giese, A., Siebert, H., et al. (1999). Evidence of presynaptic location and function of the prion protein. Journal of Neuroscience, 19, 8866–8875.

    PubMed  CAS  Google Scholar 

  • Hirokawa, N., & Takemura, R. (2005). Molecular motors and mechanisms of directional transport in neurons. Nature Reviews. Neuroscience, 6, 201–214.

    Article  PubMed  CAS  Google Scholar 

  • Hornshaw, M. P., McDermott, J. R., Candy, J. M., & Lakey, J. H. (1995). Copper binding to the N-terminal tandem repeat region of mammalian and avian prion protein: Structural studies using synthetic peptides. Biochemical and Biophysical Research Communications, 214, 993–999.

    Article  PubMed  CAS  Google Scholar 

  • Hundt, C., Gauczynski, S., Leucht, C., Riley, M. L., & Weiss, S. (2003). Intra- and interspecies interactions between prion proteins and effects of mutations and polymorphisms. Biological Chemistry, 384, 791–803.

    Article  PubMed  CAS  Google Scholar 

  • Hundt, C., Peyrin, J. M., Haik, S., Gauczynski, S., Leucht, C., Rieger, R., et al. (2001). Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor. EMBO Journal, 20, 5876–5886.

    Article  PubMed  CAS  Google Scholar 

  • Kretzschmar, H. A., Tings, T., Madlung, A., Giese, A., & Herms, J. (2000). Function of PrPC as a copper-binding protein at the synapse. Archives of Virology Supplementum, 16, 239–249.

    Google Scholar 

  • Laine, J., Marc, M. E., Sy, M. S., & Axelrad, H. (2001). Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum. European Journal of Neuroscience, 14, 47–56.

    Article  PubMed  CAS  Google Scholar 

  • Lindquist, S. L. (2002–2003). Prion proteins: One surprise after another. Harvey Lectures, 98, 173–205.

    Google Scholar 

  • Lopez Garcia, F., Zahn, R., Riek, R., & Wuthrich, K. (2000). NMR structure of the bovine prion protein. Proceedings of the National Academy of Sciences of the United States of America, 97, 8334–8339.

    Article  PubMed  CAS  Google Scholar 

  • Mange, A., Milhavet, O., Umlauf, D., Harris, D., & Lehmann, S. (2002). PrP-dependent cell adhesion in N2a neuroblastoma cells. FEBS Letters, 514, 159–162.

    Article  PubMed  CAS  Google Scholar 

  • Mironov, Jr., A., Latawiec, D., Wille, H., Bouzamondo-Bernstein, E., Legname, G., Williamson, R. A., et al. (2003). Cytosolic prion protein in neurons. Journal of Neuroscience, 23, 7183–7193.

    PubMed  CAS  Google Scholar 

  • Mouillet-Richard, S., Ermonval, M., Chebassier, C., Laplanche, J. L., Lehmann, S., Launay, J. M., et al. (2000). Signal transduction through prion protein. Science, 289, 1925–1928.

    Article  PubMed  CAS  Google Scholar 

  • Moya, K. L., Hässig, R., Breen, K. C., Volland, H., & Di Giamberardino, L. (2005). Axonal transport of the cellular prion protein is increased during axon regeneration. Journal of Neurochemistry, 92, 1044–1053.

    Article  PubMed  CAS  Google Scholar 

  • Moya, K. L., Hässig, R., Créminon, C., Laffont, I., & Di Giamberardino, L. (2004). Enhanced detection and retrograde axonal transport of PrPC in peripheral nerve. Journal of Neurochemistry, 88, 155–160.

    Article  PubMed  CAS  Google Scholar 

  • Pauly, P. C., & Harris, D. A. (1998). Copper stimulates endocytosis of the prion protein. Journal of Biological Chemistry, 273, 33107–3310.

    Article  PubMed  CAS  Google Scholar 

  • Perera, W. S., & Hooper, N. M. (2001). Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region. Current Biology, 11, 519–523.

    Article  PubMed  CAS  Google Scholar 

  • Piccardo, P., Safar, J., Ceroni, M., Gajdusek, D. C., & Gibbs Jr., C. J. (1990). Immunohistochemical localization of prion protein in spongiform encephalopathies and normal brain tissue. Neurology, 40, 518–522.

    PubMed  CAS  Google Scholar 

  • Rachidi, W., Mange, A., Senator, A., Guiraud, P., Riondel, J., Benboubetra, M., et al. (2003b). Prion infection impairs copper binding of cultured cells. Journal of Biological Chemistry, 278, 14595–14598 (Epub 2003 Mar 10).

    Article  CAS  Google Scholar 

  • Rachidi, W., Vilette, D., Guiraud, P., Arlotto, M., Riondel, J., Laude, H., et al. (2003a). Expression of prion protein increases cellular copper binding and antioxidant enzyme activities but not copper delivery. Journal of Biological Chemistry, 278, 9064–9072 (Epub 2002 Dec 23).

    Article  CAS  Google Scholar 

  • Rahman, A., Friedman, D. S., & Goldstein, L. S. (1998). Two kinesin light chain genes in mice. Identification and characterization of the encoded proteins. Journal of Biological Chemistry, 273, 15395–15403.

    Article  PubMed  CAS  Google Scholar 

  • Riek, R., Hornemann, S., Wider, G., Glockshuber, R., & Wuthrich, K. (1997). NMR characterization of the full-length recombinant murine prion protein, mPrP(23–231). FEBS Letters, 413, 282–288.

    Article  PubMed  CAS  Google Scholar 

  • Rodolfo, K., Hässig, R., Moya, K. L., Frobert, Y., Grassi, J., & Di Giamberardino, L. (1999). A novel cellular prion protein isoform present in rapid anterograde axonal transport. NeuroReport, 10, 3639–3644.

    Article  PubMed  CAS  Google Scholar 

  • Roucou, X., Gains, M., & LeBlanc, A. C. (2004). Neuroprotective functions of prion protein. Journal of Neuroscience Research, 75, 153–161.

    Article  PubMed  CAS  Google Scholar 

  • Safar, J., Ceroni, M., Piccardo, P., Liberski, P. P., Miyazaki, M., Gajdusek, D. C., et al. (1990). Subcellular distribution and physicochemical properties of scrapie-associated precursor protein and relationship with scrapie agent. Neurology, 40, 503–508.

    PubMed  CAS  Google Scholar 

  • Sáles, N., Hassig, R., Rodolfo, K., Di Giamberardino, L., Traiffort, E., Ruat, M., et al. (2002). Developmental expression of the cellular prion protein in elongating axons. European Journal of Neuroscience, 15, 1163–1177.

    Article  PubMed  Google Scholar 

  • Sáles, N., Rodolfo, K., Hassig, R., Faucheux, B., Di Giamberardino, L., & Moya, K. L. (1998). Cellular prion protein localization in rodent and primate brain. European Journal of Neuroscience, 10, 2464–2471.

    Article  PubMed  Google Scholar 

  • Santuccione, A., Sytnyk, V., Leshchyns’ka, I., & Schachner, M. (2005). Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. Journal of Cell Biology, 169, 341–354.

    Article  PubMed  CAS  Google Scholar 

  • Schachner, M., & Martini, R. (1995). Glycans and the modulation of neural-recognition molecule function. Proceedings of the National Academy of Sciences of the United States of America, 84, 6934–6938.

    Google Scholar 

  • Shorter, J., Lindquist, S. (2005). Prions as adaptive conduits of memory and inheritance. Nature Reviews. Genetics, 6, 435–450.

    Article  PubMed  CAS  Google Scholar 

  • Si, K., Lindquist, S., & Kandel, E. R. (2003). A neuronal isoform of the aplysia CPEB has prion-like properties. Cell, 115, 879–891.

    Article  PubMed  CAS  Google Scholar 

  • Stahl, N., Borchelt, D. R., Hsiao, K., & Prusiner, S. B. (1987). Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell, 51, 229–240.

    Article  PubMed  CAS  Google Scholar 

  • Vassallo, N., & Herms, J. (2003). Cellular prion protein function in copper homeostasis and redox signalling at the synapse. Journal of Neurochemistry, 86, 538–544.

    Article  PubMed  CAS  Google Scholar 

  • Voshol, H., van Zuylen, C. W. E. M., Orberger, G., Vliegenthart, J. F. G., & Schachner, M. (1996). Structure of the HNK-1 carbohydrate epitope on bovine peripheral myelin glycoprotein P0. Journal of Biological Chemistry, 38, 22957–22960.

    Google Scholar 

  • Warner, R. G., Hundt, C., Weiss, S., & Turnbull, J. E. (2002). Identification of the heparan sulfate binding sites in the cellular prion protein. Journal of Biological Chemistry, 277, 18421–18430.

    Article  PubMed  CAS  Google Scholar 

  • Wickner, R. B., Edskes, H. K., Ross, E. D., Pierce, M. M., Shewmaker, F., Baxa, U., et al. (2004). Prions of yeast are genes made of protein: Amyloids and enzymes. Cold Spring Harbor Symposia on Quantitative Biology, 69, 489–496.

    Article  PubMed  CAS  Google Scholar 

  • Wong, B. S., Chen, S. G., Colucci, M., Xie, Z., Pan, T., Liu, T., et al. (2001). Aberrant metal binding by prion protein in human prion disease. Journal of Neurochemistry, 78, 1400–1408.

    Article  PubMed  CAS  Google Scholar 

  • Zahn, R., Liu, A., Luhrs, T., Riek, R., von Schroetter, C., Lopez Garcia, F., et al. (2000). NMR solution structure of the human prion protein. Proceedings of the National Academy of Sciences of the United States of America, 97, 145–150.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sandra E. Encalada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Encalada, S.E., Moya, K.L., Lehmann, S. et al. The Role of the Prion Protein in the Molecular Basis for Synaptic Plasticity and Nervous System Development. J Mol Neurosci 34, 9–15 (2008). https://doi.org/10.1007/s12031-007-0011-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-007-0011-x

Keywords

Navigation