Superactivation of glutamate receptors by auxiliary proteins

old_uid14630
titleSuperactivation of glutamate receptors by auxiliary proteins
start_date2014/11/14
schedule11h30
onlineno
detailsSéminaire FBN. Une invitation de Daniel Choquet, Directeur l'IINS
summaryPostsynaptic glutamate receptors found at synapses between nerve cells are essential for brain function. The activation of these complex macromolecular machines is triggered by neurotransmitters in a fraction of a second. We identified a hotspot which controls both gating and their ability to follow fast signaling in a highly coupled fashion. This coupling was rather unexpected at the molecular level, but made sense in terms of signaling in the brain. This work generated tools that allowed us to investigate how glutamate receptor complexes incorporating auxiliary proteins are activated. Based on these experiments, we propose a simple activation mechanism with striking implications for short-term synaptic plasticity. In addition to investigating the activation of glutamate receptors, we have become interested in engineering receptors to be light sensitive, or to report their activity with a fluorescence signal. Various methods are available for inactivation of neuronal pathways, from knockouts to RNA interference and pharmacology. All these methods are rather slow, which can make inference about mechanism difficult. We have achieved complete light-driven acute inactivation of glutamate receptors within a couple of seconds using genetically-encoded unnatural amino acids. This approach should be generally applicable to other receptors and proteins in native tissue.
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