title: A GluD Coming-Of-Age Story.
abstract: The GluD1 and GluD2 receptors form the GluD ionotropic glutamate receptor (iGluR) subfamily. Without known endogenous ligands, they have long been referred to as 'orphan' and remained enigmatic functionally. Recent progress has, however, radically changed this view. Both GluD receptors are expressed in wider brain regions than originally thought. Human genetic studies and analyses of knockout mice have revealed their involvement in multiple neurodevelopmental and psychiatric disorders. The discovery of endogenous ligands, together with structural investigations, has opened the way towards a mechanistic understanding of GluD signaling at central nervous system synapses. These studies have also prompted the hypothesis that all iGluRs, and potentially other neurotransmitter receptors, rely on the cooperative binding of extracellular small-molecule and protein ligands for physiological signaling.
authors.affiliation: Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: myuzaki@a5.keio.jp.
authors.forename: Michisuke
authors.initials: M
authors.lastname: Yuzaki
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: A Radu
authors.initials: AR
authors.lastname: Aricescu
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006801:Humans; D013569:Synapses / Q000201:enzymology
chemical_list: D005969:Glutamate Dehydrogenase