title: Retour aux sources: defining the structural basis of glutamate receptor activation.
abstract: Ionotropic glutamate receptors (iGluRs) are the major excitatory neurotransmitter receptor in the vertebrate CNS and, as a result, their activation properties lie at the heart of much of the neuronal network activity observed in the developing and adult brain. iGluRs have also been implicated in many nervous system disorders associated with postnatal development (e.g. autism, schizophrenia), cerebral insult (e.g. stroke, epilepsy), and disorders of the ageing brain (e.g. Alzheimer's disease, Parkinsonism). In view of this, an emphasis has been placed on understanding how iGluRs activate and desensitize in functional and structural terms. Early structural models of iGluRs suggested that the strength of the agonist response was primarily governed by the degree of closure induced in the ligand-binding domain (LBD). However, recent studies have suggested a more nuanced role for the LBD with current evidence identifying the iGluR LBD interface as a "hotspot" regulating agonist behaviour. Such ideas remain to be consolidated with recently solved structures of full-length iGluRs to account for the global changes that underlie channel activation and desensitization.
authors.affiliation: Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada; Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
authors.forename: G Brent
authors.initials: GB
authors.lastname: Dawe
authors.forename: Mark R
authors.initials: MR
authors.lastname: Aurousseau
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Daniels
authors.forename: Derek
authors.initials: D
authors.lastname: Bowie
mesh_terms: D000818:Animals; D001665:Binding Sites; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate