The group led by Dr. Giménez Martín study the pathophysiology of glutamatergic and glycinergic pathways in the central nervous system. They are experts in neurotransmission mediated by glutamate and glycine and related affected disorders such as schizophrenia or hyperekplexia, respectively. The group is interested in:
• Find SLC6A5 polymorphisms (the glycine transporter GLYT2) Diagnosed in patients with hyperekplexia (in collaboration with Dr. Paul D. Lapunzina, Hospital La Paz, Madrid).
• Establishing the causes of inactivity on polymorphisms of GLYT2 Associated with hyperekplexia, and the effects of mutations on GLYT2 molecular architecture in original. Study of the biogenesis and intracellular trafficking mutants of the human orthologs whose have been described as responsible for hyperekplexia.
• Since 2010, the group is studying mutations in the geneencoding the sodium channel Nav1.1 involved in severe epilepsy type Dravet Syndrome. So far, 486 patients info we have analyzed with the group of Hospital La Paz mentioned above, and we are studying the effects of mutations on the intracellular in original trafficking of the channel.
• Study of the glycine-mediated neurotransmission in the brain stem and spinal cord. Neuromuscular system disorders related glycinergic system: hiperekplexia.
• Molecular basis of processes involved glutamatergic neurotransmission in memory, learning and in pathological neurodegenerative diseases: such as processes. Our interest is in the study of glutamatergic hypothesis of schizophrenia.
• Severe myoclonic epilepsy or Dravet syndrome (DS) is caused by mutations in the gene encoding SCN1A voltage-gated sodium channel alpha-1 subunit. Some of these mutations can affect channel properties, but another could be related to alterations in intracellular protein trafficking. Therefore, we also intend to investigate the intracellular trafficking of some of these mutant channels. Accordingly, our work plan is: the analysis of the electrical properties of the mutants inheterologous expression system using electrophysiological recording.
Preparation of expression vectors for wild type and mutant channels in neurons. These vectors are based on the Sindbis virus. Analysis of cell trafficking from the intracellular compartments to the cell surface, and the lateral mobility of the channels. For this porpoise we will confocal and multiphoton microscopy. Study of the interaction of the wild type and mutant forms of NaV1.1 associated with proteins involved in the traffic channel. We will use biochemical and cell biology techniques. NaV1.1 traffic regulation by ubiquitylation/ desubiquitilation and the possible role of other regulators in the modification (sumoylation, neddylation) by biochemical techniques.