Differential assembly of coexpressed glutamate receptor subunits in neurons of rat cerebral cortex.
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.
Brose
N
N
Salk Institute, Molecular Neurobiology Laboratory, La Jolla, California 92037.
Huntley
G W
GW
Stern-Bach
Y
Y
Sharma
G
G
Morrison
J H
JH
Heinemann
S F
SF
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002846:Chromatography, Affinity; D015870:Gene Expression; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000032:analysis / Q000302:isolation & purification; D017470:Receptors, Glutamate / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D018092:Kainic Acid Receptors / Q000032:analysis / Q000302:isolation & purification; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D046911:Macromolecular Substances; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate