Juan Lerma

Biography

Professor Juan Lerma Instituto de Neurociencias CSIC-UMH – The Instituto de Neurociencias de Alicante

Research Interest

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.