title: Metabotropic glutamate receptors and interacting proteins: evolving drug targets.
abstract: The correct targeting, localization, regulation and signaling of metabotropic glutamate receptors (mGluRs) represent major mechanisms underlying the complex function of neuronal networks. These tasks are accomplished by the formation of synaptic signal complexes that integrate functionally related proteins such as neurotransmitter receptors, enzymes and scaffold proteins. By these means, proteins interacting with mGluRs are important regulators of glutamatergic neurotransmission. Most described mGluR interaction partners bind to the intracellular C-termini of the receptors. These domains are extensively spliced and phosphorylated, resulting in a high variability of binding surfaces offered to interacting proteins. Malfunction of mGluRs and associated proteins are linked to neurodegenerative and neuropsychiatric disorders including addiction, depression, epilepsy, schizophrenia, Alzheimer's, Huntington's and Parkinson's disease. MGluR associated signal complexes are dynamic structures that assemble and disassemble in response to the neuronal fate. This, in principle, allows therapeutic intervention, defining mGluRs and interacting proteins as promising drug targets. In the last years, several studies elucidated the geometry of mGluRs in contact with regulatory proteins, providing a solid fundament for the development of new therapeutic strategies. Here, I will give an overview of human disorders directly associated with mGluR malfunction, provide an up-to-date summary of mGluR interacting proteins and highlight recently described structures of mGluR domains in contact with binding partners.
authors.affiliation: Institut fur Biochemie, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Fahrstr. 17, 91054 Erlangen, Germany. ralf.enz@biochem.uni-erlangen.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Enz
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D018683:Excitatory Amino Acid Agents / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate