Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer
Top Cited Papers
- 1 June 2001
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 411 (6840) , 962-965
- https://doi.org/10.1038/35082096
Abstract
G-protein-coupled receptors (GPCRs) transduce signals from extracellular transmitters to the inside of the cell by activating G proteins. Mutation and overexpression of these receptors have revealed that they can reach their active state even in the absence of agonist, as a result of a natural shift in the equilibrium between their inactive and active conformations1. Such agonist-independent (constitutive) activity has been observed for the glutamate GPCRs (the metabotropic glutamate receptors mGluR1a and mGluR5) when they are overexpressed in heterologous cells2. Here we show that in neurons, the constitutive activity of these receptors is controlled by Homer proteins, which bind directly to the receptors' carboxy-terminal intracellular domains3,4. Disruption of this interaction by mutagenesis or antisense strategies, or expression of endogenous Homer1a (H1a), induces constitutive activity in mGluR1a or mGluR5. Our results show that these glutamate GPCRs can be directly activated by intracellular proteins as well as by agonists.Keywords
This publication has 24 references indexed in Scilit:
- Constitutively active mutants of 5‐HT 4 receptors are they in unique active states?EMBO Reports, 2001
- Mapping the Agonist-binding Site of GABAB Type 1 Subunit Sheds Light on the Activation Process of GABABReceptorsPublished by Elsevier ,2000
- The Non-competitive Antagonists 2-Methyl-6-(phenylethynyl)pyridine and 7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic Acid Ethyl Ester Interact with Overlapping Binding Pockets in the Transmembrane Region of Group I Metabotropic Glutamate ReceptorsJournal of Biological Chemistry, 2000
- Homer 1b Regulates the Trafficking of Group I Metabotropic Glutamate ReceptorsPublished by Elsevier ,1999
- Homer: a protein that selectively binds metabotropic glutamate receptorsNature, 1997
- Two Isoforms of the Prostaglandin E Receptor EP3 Subtype Different in Agonist-independent Constitutive ActivityPublished by Elsevier ,1996
- Truncation of the Thyrotropin-releasing Hormone Receptor Carboxyl Tail Causes Constitutive Activity and Leads to Impaired Responsiveness in Xenopus Oocytes and AtT20 CellsPublished by Elsevier ,1995
- Activation of a Large‐conductance Ca2+‐Dependent K+ Channel by Stimulation of Glutamate Phosphoinositide‐coupled Receptors in Cultured Cerebellar Granule CellsEuropean Journal of Neuroscience, 1991
- Coupling of Inositol Phospholipid Metabolism with Excitatory Amino Acid Recognition Sites in Rat HippocampusJournal of Neurochemistry, 1986
- Glutamate stimulates inositol phosphate formation in striatal neuronesNature, 1985