Pentameric subunit stoichiometry of a neuronal glutamate receptor.
Ionotropic glutamate receptors, neurotransmitter-activated ion channels that mediate excitatory synaptic transmission in the central nervous system, are oligomeric membrane proteins of unknown subunit stoichiometry. To determine the subunit stoichiometry we have used a functional assay based on the blockade of two alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor subunit 1 (GluR1) mutant subunits selectively engineered to exhibit differential sensitivity to the open channel blockers phencyclidine and dizolcipine (MK-801). Coinjection into amphibian oocytes of weakly sensitive with highly sensitive subunit complementary RNAs produces functional heteromeric channels with mixed blocker sensitivities. Increasing the fraction of the highly sensitive subunit augmented the proportion of drug-sensitive receptors. Analysis of the data using a model based on random aggregation of receptor subunits allowed us to determine a pentameric stoichiometry for GluR1. This finding supports the view that a pentameric subunit organization underlies the structure of the neuronal ionotropic glutamate receptor gene family.
Ferrer-Montiel
A V
AV
Department of Biology, University of California at San Diego, La Jolla 92093-0366, USA.
Montal
M
M
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010622:Phencyclidine / Q000494:pharmacology; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014981:Xenopus
D016291:Dizocilpine Maleate; D007608:Kainic Acid; D046911:Macromolecular Substances; D010622:Phencyclidine; D018091:Receptors, AMPA; D011994:Recombinant Proteins