Medical Journals

The Metabotropic Glutamate G-protein-coupled Receptors Mglur3 and Mglur1a Are Voltage-sensitive.

Authors:
  • Ohana Lily
  • Barchad Ofra
  • Parnas Itzchak
  • Parnas Hanna

From: Department of Neurobiology, the Hebrew University, Jerusalem 91904, Israel. hanna@vms.huji.ac.il

The Journal of biological chemistry

  • Publish Date: Aug 2006
  • ISSN: 0021-9258
  • Volume: 281
  • Issue: 34
  • Pages: 24204-15
  • Medium: Print
  • Language: English
  • Citation (JAMA): Ohana Lily, Barchad Ofra, Parnas Itzchak, et al. The Metabotropic Glutamate G-protein-coupled Receptors Mglur3 and Mglur1a Are Voltage-sensitive.. J. Biol. Chem. Aug 2006;281:24204-15

Abstract

G-protein-coupled receptors play a key role in signal transduction processes. Despite G-protein-coupled receptors being transmembrane proteins, the notion that they exhibit voltage sensitivity is rather novel. Here we examine whether two metabotropic glutamate receptors, mGluR3 and mGluR1a, both involved in fundamental physiological processes, exhibit, by themselves, voltage sensitivity. Measuring mGluR3-induced K(+) currents and mGluR1a-induced Ca(2+)-activated Cl(-) currents in Xenopus oocytes, we show that the apparent affinity toward glutamate decreases (mGluR3) or increases (mGluR1a) upon depolarization. Measurements of binding of [(3)H]glutamate to oocytes expressing either mGluR3 or mGluR1a corroborated the electrophysiological results. Using the chimeric Galpha subunit, we further show that the voltage sensitivity does not reside in the G-protein. To locate sites within the receptors that are involved in the voltage sensitivity, we used chimeric mGluR1a, where the intracellular loops that couple to the G-protein were replaced by those of mGluR3. The voltage sensitivity of the chimeric mGluR1a resembled that of mGluR3 and not that of the parental mGluR1a. The cumulative results indicate that the voltage sensitivity does not reside downstream to the activation of the receptors but rather in the mGluR3 and mGluR1a themselves. Furthermore, the intracellular loops play a crucial role in relaying changes in membrane potential to changes in the affinity of the receptors toward glutamate.

Mesh Headings (Keywords): Amino Acid Motifs, Animals, GTP-Binding Proteins, Ion Channels, Ion Transport, Membrane Potentials, Rats, Receptors, G-Protein-Coupled, Receptors, Metabotropic Glutamate, Recombinant Fusion Proteins, Xenopus laevis


Check for Full Text / PubMed Unique Identifier (PMID): 16760467


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