Molecular mechanisms of central synapses

Professor Ralf Schoepfer
Professor of Pharmacology and Molecular Neuroscience
Room 414
Laboratory for Molecular Pharmacology
Tel: 020 7679 7242

Ralf Schoepfer studied Medicine and Biochemistry in Tübingen and conducted research at the Max Planck-Institute in Tübingen, The Salk Institute in LaJolla and the ZMBH in Heidelberg. He came to UCL as a Senior Wellcome Trust Fellow and is Professor of Pharmacology and Molecular Neuroscience.

Higher brain functions, including learning and memory, are based on the properties of networks of neurons, and their ability to express plasticity. The network properties in turn are the result of the interaction of cellular components and their underlying molecular machinery.

We are interested in the molecules found in synapses, the contact points between nerve cells. In particular our research focuses on the receptors for neurotransmitters, such as the family of ionotropic glutamate receptors, and their associated molecules.

Further insights into the mechanisms and pathways of synaptic function are important steps towards an understanding of a range of neurological and psychiatric disorders.

Current research

Our current research is working towards a comprehensive analysis of postsynaptic proteins, their interactions and posttranslational modification in single experiments. Large-scale and deep-reaching proteomic analysis is applied to tissue from normal and diseased brains.

We are grateful for funding from the Wellcome Trust, BBSRC and MRC.

Full publication list with PDFs

Recent Publications:

  • Edgington, R. J., Thalhammer, A., Welch, J. O., Bongrain, A.,Bergonzo, P., Scorsone, E., Jackman, R. B., and Schoepfer, R. (2013).Patterned neuronal networks using nanodiamonds and the effect of varying nanodiamond properties on neuronal adhesion and outgrowth. J Neural Eng 10, 056022.  Abstract (Link to PubMed)
  • Trinidad, J. C., Schoepfer, R., Burlingame, A. L., and Medzihradszky, K. F. (2013). N- and O-glycosylation in the murine synaptosome. Mol Cell Proteomics. E-pub 1 July 2013. Abstract (Link to PubMed)
  • Trinidad, J. C., Thalhammer, A., Burlingame, A. L., and Schoepfer, R.(2013). Activity-dependent protein dynamics define interconnectedcores of co-regulated postsynaptic proteins. Mol Cell Proteomics. 2013 Jan;12(1):29-41 Abstract (Link to Pubmed)
  • Trinidad, J. C., Barkan, D. T., Gulledge, B. F., Thalhammer, A., Sali, A., Schoepfer, R., and Burlingame, A. L. (2012). Global Identification and Characterization of Both O-GlcNAcylation and Phosphorylation at the Murine Synapse. Mol Cell Proteomics 11, 215-229. Abstract (link to PubMed)
  • Thalhammer A, Edgington RJ, Cingolani LA, Schoepfer R, and Jackman RB. (2010) The use of nanodiamond monolayer coatings to promote the formation of functional neuronal networks. Biomaterials, 31:2097-104. Abstract (link to PubMed)
  • Chen, P. E., Errington, M. L., Kneussel, M., Chen, G., Annala, A. J., Rudhard, Y., Lin, C. L., Rast, G. F., Specht, C. G., Tigaret, C. M., Nassar, M. A., Morris, R. G., Bliss, T. V., and Schoepfer, R. (2009). Behavioral deficits and subregion-specific suppression of LTP in mice expressing a population of mutant NMDA receptors throughout the hippocampus. Learning and Memory 16, 635-644. Abstract (link to PubMed)
  • Filosa A, Paixao S, Honsek SD, Carmona MA, Becker L, Feddersen B, Gaitanos L, Rudhard Y, Schoepfer R, Klopstock T, Kullander K, Rose CR, Pasquale EB and Klein R. (2009) Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nat Neurosci Epub ahead of print. Abstract (link to PubMed)
  • Chalkley, R. J., Thalhammer, A., Schoepfer, R., and Burlingame, A. L. (2009). Identification of protein OGlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptides. Proc Natl Acad Sci 106, 8894-8899. Abstract (link to PubMed)
  • Thalhammer, A., Trinidad, J. C., Burlingame, A. L., and Schoepfer, R. (2009). Densin-180: revised membrane topology, domain structure and phosphorylation status. J Neurochem. Abstract (link to PubMed)
  • Puddifoot, C. A., Chen, P. E., Schoepfer, R., and Wyllie, D. J. (2009). Pharmacological characterization of recombinant NR1/NR2A NMDA receptors with truncated and deleted carboxy termini expressed in Xenopus laevis oocytes. Br J Pharmacol 156, 509-518. Abstract (link to PubMed)
  • Medvedev, N. I., Rodriguez-Arellano, J. J., Popov, V. I., Davies, H. A., Tigaret, C. M., Schoepfer, R., and Stewart, M. G. (2008). The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus. Eur J Neurosci 27, 315-325. Abstract (link to PubMed)
  • Trinidad, J. C., Thalhammer, A., Specht, C. G., Aenoch, J. L., Baker, P. R., Schoepfer, R., and Burlingame, A. L. (2008). Quantitative analysis of synaptic phosphorylation and protein expression. Mol Cell Proteomics. Mol Cell Proteomics 7, 684-896 Abstract (link to PubMed)
  • Thalhammer, A., Rudhard, Y., Tigaret, C. M., Volynski, K. E., Rusakov, D. A., and Schoepfer, R. (2006). CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling. EMBO J. Abstract (link to PubMed)
  • Trinidad, J. C., Specht, C. G., Thalhammer, A., Schoepfer, R., and Burlingame, A. L. (2006). Comprehensive identification of phosphorylation sites in postsynaptic density preparations. Mol Cell Proteomics 5, 914-922. Abstract (Link to PubMed)
  • Vosseller, K., Trinidad, J. C., Chalkley, R. J., Specht, C. G., Thalhammer, A., Lynn, A. J., Snedecor, J. H., Guan, S., Medzihradszky, K. F., Maltby, D. A., Schoepfer, R., and Burlingame, A. L. (2006). O-GlcNAc proteomics of postsynaptic density preparations using lectin weak affinity chromatography (LWAC) and mass spectrometry. Mol Cell Proteomics 5, 923-934. Abstract (Link to PubMed)
  • Tigaret C.M., Thalhammer A, Rast G.F., Specht C.G., Auberson Y.P., Stewart M.G., Schoepfer R. (2006) Subunit dependencies of NMDA receptor-induced AMPA receptor internalization. Mol Pharm 69, 1251-125 Abstract (Link to PubMed)
  • Zhang,Y., Bo, X., Schoepfer, R., Holtmaat, A.J., Verhaagen, J., Emson P.C., Lieberman, A.R., and Anderson, P.N. (2005) Growth-associated protein GAP-43 and L1 act synergistically to promote regenerative growth of Purkinje cell axons in vivo. PNAS 102,14883-14888 Abstract (Link to PubMed)
  • Stewart, M. G., Medvedev, N. I., Popov, V. I., Schoepfer, R., Davies, H. A., Murphy, K., Dallerac, G. M., Kraev, I. V., and Rodriguez, J. J. (2005). Chemically induced long-term potentiation increases the number of perforated and complex postsynaptic densities but does not alter dendritic spine volume in CA1 of adult mouse hippocampal slices. Eur J Neurosci 21, 3368-3378. Abstract (Link to PubMed)
  • Trinidad, J. C., Thalhammer, A., Specht, C. G., Schoepfer, R., and Burlingame, A. L. (2005). Phosphorylation state of postsynaptic density proteins. J Neurochem 92, 1306-1316. Abstract (Link to PubMed)
  • Specht, C. G., Tigaret, C. M., Rast, G. F., Thalhammer, A., Rudhard, Y., and Schoepfer, R. (2005). Subcellular localisation of recombinant alpha- and gamma-synuclein. Mol Cell Neurosci 28, 326-334. Abstract (Link to PubMed)
  • Specht, C. G., and Schoepfer, R. (2004). Deletion of multimerin-1 in alpha-synuclein-deficient mice. Genomics 83, 1176-1178. Abstract (Link to PubMed)
  • Specht, C. G., Williams, O. A., Jackman, R. B., and Schoepfer, R. (2004). Ordered growth of neurons on diamond. Biomaterials 25, 4073-4078. Abstract (Link to PubMed)
  • Chen, P. E., Johnston, A. R., Mok, M. H., Schoepfer, R., and Wyllie, D. J. (2004). Influence of a threonine residue in the S2 ligand binding domain in determining agonist potency and deactivation rate of recombinant NR1a/NR2D NMDA receptors. J Physiol 558, 45-58. Abstract (Link to PubMed)
  • Bliss, T., and Schoepfer, R. (2004). Controlling the ups and downs of synaptic strength. Science 304, 973-974. Abstract (Link to PubMed)
  • Rudhard, Y., Kneussel, M., Nassar, M. A., Rast, G. F., Annala, A. J., Chen, P. E., Tigaret, C. M., Dean, I., Roes, J., Gibb, A. J., Hunt, S. P., and Schoepfer, R. (2003). Absence of Whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling. J Neurosci 23, 2323-2332. Abstract (Link to PubMed)
  • Bo, X., Kim, M., Nori, S. L., Schoepfer, R., Burnstock, G., and North, R. A. (2003). Tissue distribution of P2X4 receptors studied with an ectodomain antibody. Cell Tissue Res 313, 159-165. Abstract (Link to PubMed)
  • Chen, P. E., Specht, C. G., Morris, R. G., and Schoepfer, R. (2002). Spatial learning is unimpaired in mice containing a deletion of the alpha-synuclein locus. Eur J Neurosci 16, 154-158. Abstract (Link to PubMed)
  • Specht, C. G., and Schoepfer, R. (2001). Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2, 11. Abstract (Link to PubMed)
  • Bo, X., Liu, M., Schoepfer, R., and Burnstock, G. (2001). Characterization and expression of ATP P2X4 receptor from embryonic chick skeletal muscle. Drug Development Research 53, 22 - 28. Abstract (Link to PubMed)
  • Bo, X., Schoepfer, R., and Burnstock, G. (2000). Molecular cloning and characterization of a novel ATP P2X receptor subtype from embryonic chick skeletal muscle. J Biol Chem 275, 14401-14407. Abstract (Link to PubMed)
  • Anson, L. C., Schoepfer, R., Colquhoun, D., and Wyllie, D. J. (2000). Single-channel analysis of an NMDA receptor possessing a mutation in the region of the glutamate binding site. J Physiol 527 Pt 2, 225-237. Abstract (Link to PubMed)

Selected older publications:

  • Anson, L. C., Chen, P. E., Wyllie, D. J., Colquhoun, D., and Schoepfer, R. (1998). Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors. J Neurosci 18, 581-589. Abstract (Link to PubMed)
  • Lewis, T. M., Sivilotti, L. G., Colquhoun, D., Gardiner, R. M., Schoepfer, R., and Rees, M. (1998). Properties of human glycine receptors containing the hyperekplexia mutation alpha1(K276E), expressed in Xenopus oocytes. J Physiol London 507, 25-40. Abstract (Link to PubMed)
  • Laurie, D. J., Bartke, I., Schoepfer, R., Naujoks, K., and Seeburg, P. H. (1997). Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Brain Res Mol Brain Res 51, 23-32. Abstract (Link to PubMed)
  • Wyllie, D. J., Behe, P., Nassar, M., Schoepfer, R., and Colquhoun, D. (1996). Single-channel currents from recombinant NMDA NR1a/NR2D receptors expressed in Xenopus oocytes. Proc R Soc Lond B Biol Sci 263, 1079-1086. Abstract (Link to PubMed)
  • Kuner, T., and Schoepfer, R. (1996). Multiple structural elements determine subunit specificity of Mg 2+ block in NMDA receptor channels. J Neurosci 16, 3549-3558. Abstract (Link to PubMed)
  • Bo, X., Zhang, Y., Nassar, M., Burnstock, G., and Schoepfer, R. (1995). A P2X purinoceptor cDNA conferring a novel pharmacological profile. FEBS Lett 375, 129-133. Abstract (Link to PubMed)
  • Behe, P., Stern, P., Wyllie, D. J., Nassar, M., Schoepfer, R., and Colquhoun, D. (1995). Determination of NMDA NR1 subunit copy number in recombinant NMDA receptors. Proc R Soc Lond B Biol Sci 262, 205-213. Abstract (Link to PubMed)
  • Mosbacher, J., Schoepfer, R., Monyer, H., Burnashev, N., Seeburg, P. H., and Ruppersberg, J. P. (1994). A molecular determinant for submillisecond desensitization in glutamate receptors. Science 266, 1059-1062. Abstract (Link to PubMed)
  • Schoepfer, R. (1993). The pRSET family of T7 promoter expression vectors for Escherichia coli. Gene 124, 83-85. Abstract (Link to PubMed)
  • Raditsch, M., Ruppersberg, J. P., Kuner, T., Gunther, W., Schoepfer, R., Seeburg, P. H., Jahn, W., and Witzemann, V. (1993). Subunit-specific block of cloned NMDA receptors by argiotoxin636. Febs Lett 324, 63-66. Abstract (Link to PubMed)
  • Keyser, K. T., Britto, L. R., Schoepfer, R., Whiting, P., Cooper, J., Conroy, W., Brozozowska, P. A., Karten, H. J., and Lindstrom, J. (1993). Three subtypes of alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors are expressed in chick retina. J Neurosci 13, 442-454. Abstract (Link to PubMed)
  • Herlitze, S., Raditsch, M., Ruppersberg, J. P., Jahn, W., Monyer, H., Schoepfer, R., and Witzemann, V. (1993). Argiotoxin detects molecular differences in AMPA receptor channels. Neuron 10, 1131-1140. Abstract (Link to PubMed)
  • Burnashev, N., Schoepfer, R., Monyer, H., Ruppersberg, J. P., Gunther, W., Seeburg, P. H., and Sakmann, B. (1992). Control by asparagine residues of calcium permeability and magnesium blockade in the NMDA receptor. Science 257, 1415-1419. Abstract (Link to PubMed)
  • Stern, P., Behe, P., Schoepfer, R., and Colquhoun, D. (1992). Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proc R Soc Lond Biol 250, 271-277. Abstract (Link to PubMed)
  • Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B., and Seeburg, P. H. (1992). Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256, 1217-1221. Abstract (Link to PubMed)
  • Melms, A., Malcherek, G., Gern, U., Wietholter, H., Muller, C. A., Schoepfer, R., and Lindstrom, J. (1992). T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: heterogeneity of antigenic sites on the alpha-subunit. Ann Neurol 31, 311-318. Abstract (Link to PubMed)
  • Whiting, P. J., Schoepfer, R., Conroy, W. G., Gore, M. J., Keyser, K. T., Shimasaki, S., Esch, F., and Lindstrom, J. M. (1991). Expression of nicotinic acetylcholine receptor subtypes in brain and retina. Brain Res Mol Brain Res 10, 61-70. Abstract (Link to PubMed)
  • Whiting, P., Schoepfer, R., Lindstrom, J., and Priestley, T. (1991). Structural and pharmacological characterization of the major brain nicotinic acetylcholine receptor subtype stably expressed in mouse fibroblasts. Mol Pharmacol 40, 463-472. Abstract (Link to PubMed)
  • Anand, R., Conroy, W. G., Schoepfer, R., Whiting, P., and Lindstrom, J. (1991). Neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes have a pentameric quaternary structure. J Biol Chem 266, 11192-11198. Abstract (Link to PubMed)
  • Schoepfer, R., Conroy, W. G., Whiting, P., Gore, M., and Lindstrom, J. (1990). Brain alpha-bungarotoxin binding protein cDNAs and MAbs reveal subtypes of this branch of the ligand-gated ion channel gene superfamily. Neuron 5, 35-48. [The subunits originally named alphaBgtBP 1 and 2 have been renamed to nAChR alpha 7 and alpha 8, respectively]. Abstract (Link to PubMed)
  • Schoepfer, R., Halvorsen, S. W., Conroy, W. G., Whiting, P., and Lindstrom, J. (1989). Antisera against an acetylcholine receptor alpha 3 fusion protein bind to ganglionic but not to brain nicotinic acetylcholine receptors. Febs Lett 257, 393-399. Abstract (Link to PubMed)
  • Schoepfer, R., Whiting, P., Esch, F., Blacher, R., Shimasaki, S., and Lindstrom, J. (1988). cDNA clones coding for the structural subunit of a chicken brain nicotinic acetylcholine receptor. Neuron 1, 241-248. Abstract (Link to PubMed)