Abstract
In the rat, subunits of the glutamate receptor family fall into three pharmacologically distinct groups: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid preferring receptors (Glu R1-4), kainate preferring receptors (Glu R5-7, KA 1, KA 2), and N-methyl-D-aspartate preferring receptors (NMDA R1, NMDA R2A-2D). In the present study, we demonstrate immunocytochemically that the majority of neurons in rat cerebral cortex coexpress members of all three groups of glutamate receptor subunits, Glu R2/3, Glu R5/6/7, and NMDA R1. Using immunoaffinity purified or immunoprecipitated alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, kainate and N-methyl-D-aspartate receptors, we show that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors containing Glu R1-4, kainate receptors containing Glu R6, Glu R7, and KA 2 and N-methyl-D-aspartate receptors containing NMDA R1 each form distinct protein complexes that do not share subunits. Our data indicate that a mechanism exists which allows for the specific assembly of selected glutamate receptor subunits into functionally and structurally distinct heteromeric receptors.
Highlights
In the rat, subunits of the glutamate receptor family and 3) N-methybaspartate (NMDA) receptors (NMDA R1, fall into three pharmacologically distinct groups: a-amNi-MDA R2A-2D)
Ionotropic glutamate receptors are thought btoe the princi- NMDA R1 wasshownto form heteromericreceptorswith pal mediators of fast synaptic excitation in the vertebracteen- NMDA R2A-2D [18,19,20,21]. tral nervous system.Triggered by the expression cloningof the In the presesnttudy, we examined the subunciotmposition of first glutamate receptor (Glu R1) from rat brain (l),a large native glutamate receptors from rat cerebral cortex
We demonstrate that the majority of neurons inrat cerebral cortex coexpress members of all groups of glutamate receptors (Fig.2)
Summary
Ferase in frame with NMDA R1 residues 660-811 (representingthe intracellularloop betweenputative transmembraneregions I11 and Iv; residue numbers as in Ref. 24) Both antibodies recognize a protein of 116kDa in Western blotsof rat brain synaptic plasma membranes and humanembryonickidney293cells transfectedwith the NMDA R1 clone. Additional experiments indicate that the antibody is specific for Glu R2 on Western blots but recognizes Glu R2 and Glu R4 (but notGlu R1or Glu R 3 ) in immunoprecipitation^.^ The characteristics of the monoclonal antibody directed against GluR5/6/7 (clone 4F5) have been published previously [27].Aflinity purified polyclonal antibodies directed against Glu R1(4)G, lu R2/3, Glu R4 [28]a, nd Glu R6/7 [29] were a gift of Drs Craig Blackstone and Richard Huganir (Baltimore, MD).Affinity purified antibodies directed againsKtA 2 [30] were a gift of Dr Robert Wenthold (Bethesda, MD).
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