Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouse.
Glutamate is the primary excitatory neurotransmitter in the brain, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptors mediate most fast synaptic transmission. AMPA receptors are tetrameric assemblies composed from four possible subunits (GluR1-4). In hippocampal pyramidal cells, AMPA receptors are heteromeric receptors containing the GluR2 subunit and either GluR1 or GluR3. It is generally accepted that the trafficking of GluR1/GluR2 receptors to synapses requires activity, whereas GluR2/GluR3 receptors traffic constitutively. It has been suggested that the trafficking is governed by the cytoplasmic C termini of the subunits. Because the basis for this theory relied on the introduction of unnatural, homomeric, calcium-permeable AMPA receptors, we have used the GluR2(-/-) knock out mouse to determine whether the expression of mutated forms of GluR2 can rescue WT synaptic responses. We find that GluR2, lacking its entire C terminus, or a GluR2 chimera containing the C terminus of GluR1, is capable of trafficking to the synapse in the absence of activity. These findings suggest that the GluR2 C terminus is not required for GluR2 synaptic insertion.
Panicker
Sandip
S
Department of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, CA 94143, USA.
Brown
Keith
K
Nicoll
Roger A
RA
D000818:Animals; D004594:Electrophysiology; D004964:Estriol / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D021122:Protein Subunits; D018091:Receptors, AMPA; C009341:estriol succinate; D004964:Estriol; C104722:glutamate receptor ionotropic, AMPA 2