We are working on the structure and function of glutamate receptors, the most important signalling system in the brain. We analysed one important characteristic of neurotransmitter receptors: desensitization (Neuron 1992); defined its structural determinants (Neuron, 1998a) and the allosteric mechanism involved (Neuron, 2001), intrinsic to the NMDA type of glutamate receptors. We were first describing the existence in central neurons of functional kainate receptors (KARs), demonstrating that KAR proteins form functional receptor channels in hippocampal neurons (PNAS 1993) and providing the tool for further studies, the drug 2-3-benzodiazepine, GYKI 53655, which allowed their pharmacological isolation (Neuron 1995a). This finding PAVED THE WAY FOR PROGRESS IN THE FIELD. We were among the pioneers in applying single-cell RT-PCR (Neuron, 1995b) to study these receptors and described their fundamental role in controlling neuronal tissue excitability and epileptogenesis (Neuron, 1997). Also demonstrated that KARs have a dual mechanism of signalling: as ion channels and triggering a second messenger cascade, involving a G-protein (Neuron, 1998b; PNAS 2000). This and subsequent work (Neuron, 2003; EMBO J., 2007; J. Neurosci., 2013) put forward the new concept that ion channel-forming receptors are also able to signal through a G-protein, opening new vistas on the functional mechanisms of ionotropic glutamate receptors. We therefore seek to identify the elements involved in such a pathway as well as to define their functional role in brain physiology and pathology. We are currently identifying proteins interacting with KAR subunits (e.g. Neuron, 2009) by using a proteomic approach and assessing the role of these proteins by biochemical, electrophysiological and imaging experiments in brain slices, cultured neurons and in vivo experiments from normal and transgenic mice.
Please see also: htttp://in.umh.es/grupos-detalle.aspx?grupo=29
Lerma, J.& Marques JM (2013) Kainate Receptors in Health and Disease, Neuron 80, 292-311
Mire E., Mezzera C., Leyva-Díaz E., Paternain AV., Squarzoni P., Bluy E., Castillo-Paterna M., López MJ., Peregrín S., Tessier-Lavigne M., Garel S., Galcerán J., Lerma J., López-Bendito G. (2012) Spontaneous activity mediates a developmental switch in thalamocortical axon growth by regulating Robo1 transcription. Nat. Neurosci., 15 (8) : 1134–43.
Lerma J. (2011) Net(o) excitement for Kainate receptors. Nat. Neurosci. 14 (7) : 808-10.
Lau GC., Takayasu Y., Rodenas-Ruano A., Paternain AV., Lerma J., Bennett MVL., and Zukin RS. (2010) SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. J. Neurosci., 30 (1): 242–54.
Fazzari F., Paternain AV., Valiente M., Pla R., Luján R., Lloyd K., Lerma J., Marín O. and Rico B. (2010) Control of cortical GABA circuitry development by Nrg1/ErbB4 signalling. Nature 464 (7293) : 1376-80.
Selak S., Paternain AV., Aller IM., Picó E., Rivera R., Lerma J. (2009) A role for SNAP25 in internalization of kainate receptors and synaptic plasticity. Neuron 63 (3): 357-71.
Rozas, J.L., Paternain A.V. and Lerma J. (2003) Non-canonical signaling by ionotropic kainate receptors. Neuron 39, 543–553.
2011 President of Spanish Society for Neuroscience (SENC) (until today)
2011 Member of the Experts Panel, the Research and Innovation National Strategy (MICINN)
2011 Member of Academia Europaea (The Academy of Europe)
2010 Chairman of the PanEuropean Committee of IBRO (until 2013)
2010 Member of the Experts Panel of “Profarma” (MIT&MICINN)
2010 Member of FENS-IBRO European Neuroscience Schools Committee
2010 Chairman of the Western European Regional Committee of IBRO
2005 Member of European Dana Alliance for the Brain (EDAB)
2005 XI Award “Alberto Sols” to the Best Research Activity
2004 CEOE Foundation Award to the Sciences
2002 Award for Scientific Excellence “Alonso Gabriel de Herrera”
2002 Santiago Grisolía Chair Award (with Matt Mattson)
2000 Member of European Molecular Biology Organization (EMBO)
1998 Distinguished Scientist in Neurobiological Research, Health Science Foundation