Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GIuR2-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 (GIuR1-4). In hippocampal pyramidal cells, AMPA receptors are heteromeric receptors containing the GluR2 subunit and either GIuR1 or GIuR3. It is generally accepted that the trafficking of GIuR1/GIuR2 receptors to synapses requires activity, whereas GIuR2/GIuR3 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 GIuR2(-/-) knock out mouse to determine whether the expression of mutated forms of GluR2 can rescue WT synaptic responses. We find that GIuR2, lacking its entire C terminus, or a GIuR2 chimera containing the C terminus of GIuR1, is capable of trafficking to the synapse in the absence of activity. These findings suggest that the GluR2 C terminus is not required for GIuR2 synaptic insertion.