Jump Main Menu. Go directly to the main content

Sección de idiomas

EN

Fin de la sección de idiomas

Access / Registration

Sección de utilidades

Fin de la sección de utilidades

MENU
Secondary menu End of secondary menu

Research projects

Start of main content

The neuronal glycine transporter GlyT2 in herplexia: a glycinergic pathology of development

20th national competition for scientific and technical research

Rare diseases

Senior Researcher : Beatriz López Corcuera

Research Centre or Institution : Centro de Biología Molecular Severo Ochoa. CSIC - UAM

Abstract

Hyperekplexia or startle disease (OMIM 149400), is a syndrome of great relevance in the perinatal clinic. Newborns display exaggerated startle and stiffness in response to unexpected trivial stimuli, usually acoustic or tactile, which can cause respiratory failure. Babies are at risk for brain damage or even sudden death. Adults suffer disabling motor disturbances. Hyperekplexia is caused by blocking inhibitory glycinergic neurotransmission that exerts sensorimotor control in caudal regions of the central nervous system. The neuronal glycine transporter GlyT2 maintains the strength of glycinergic neurotransmission in vertebrates and its dysfunction causes a form of hyperekplexia by preventing the supply of glycine to the presynaptic neuron to follow up neurotransmission.  

In this project, we analyse how the mutations in GlyT2 found in hyperekplexia patients affect the three-dimensional structure of the transporter protein, its intracellular traffic within the neuron to reach its location on the cell surface, and its role in the development of glycinergic neurotransmission. Using bioinformatics tools such as the three dimensional models of GlyT2 structure generated by our group, we locate regions within the protein and ligands that permits us to intervene on its folding, trafficking or transport activity and thus rescue the phenotype of mutants with trafficking defects. The experimental systems we use are cell lines, primary cultures of neurons expressing wild-type GlyT2 and mutants where we study transporter biogenesis and transport activity. The electrical properties of the transporter are examined in Xenopus laevis oocytes and neurons. We also analyse the effect of GlyT2 mutations on signalling pathways that control the perinatal development of glycinergic neurotransmission both in neurons and in the in vivo system of zebrafish. Our aim is to learn the causes of inactivity of GlyT2 mutants and their consequences in development to guide future therapeutic approaches.

  • Activities related
  • Projects related
  • News related
  • Publications related

see all

End of main content