Synaptic AMPA receptor subunit trafficking is independent of the C terminus in the GluR2-lacking mouse

Abstract

Glutamate is the primary excitatory neurotransmitter in the brain, and ␣-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.

The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation

“…It has been successfully applied to all major receptor domains (30)(31)(32)(33)(34). Here, we extend this approach to the LBD of the nonfunctional delta2 subunit, providing evidence that delta2 subunits can form functional ion channels that are able to sense the conformational status of an integral LBD, i.e., that can be gated by ligands.…”

Synaptic AMPA Receptor Plasticity and Behavior

“…In brain slice preparations, only AMPARs lacking GluR1 incorporate passively into synapses (Shi et al, 2001). Studies conducted on either dissociated cultured neurons (Bats et al, 2007; Ju et al, 2004; Passafaro et al, 2001) or hippocampal slices from GluR2-deficient mice (Panicker et al, 2008) indicate that activity-independent incorporation of AMPARs can occur in a manner that is independent of c-tails. However, several results suggest this is not the case in wild-type tissue or in vivo.…”

Specific Roles of AMPA Receptor Subunit GluR1 (GluA1) Phosphorylation Sites in Regulating Synaptic Plasticity in the CA1 Region of Hippocampus

“…For example, subunits with a long intracellular carboxy terminus (i.e., GluR1, GluR2L, and GluR4) are involved in activity-dependent synaptic targeting of AMPAR, whereas those with a shorter carboxy terminus (i.e., GluR2, GluR3, and GluR4s) seem to maintain basal synaptic transmission (Kolleker et al 2003;Lee SH et al 2004;Shi et al 2001;Zhu et al 2000). However, the role of the GluR2 carboxy terminus in maintaining synaptic AMPAR is debated (Panicker et al 2008). Among the four subunits, the role of GluR1 in synaptic plasticity paradigms, such as long-term potentiation (LTP) and long-term depression (LTD), has been extensively studied.…”