Turning the current up on AMPA receptor trafficking

Abstract

Synapses that use the neurotransmitter glutamate possess both AMPA and NMDA receptors, which differ in their activation and permeation properties. AMPA receptors are hetero-oligomeric complexes comprising different combinations of four subunits, GluR1–GluR4 (also known as GluR A–D). NMDA receptors (NR1, NR2A-D, NR3A) are relatively stable on the cell surface, whereas recent evidence suggests that AMPA ligand-gated receptors recycle continuously between the plasma membrane and intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent endocytosis. Malinow and colleagues now suggest a model 1xSubunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Shi, S.-H. et al. Cell. 2001; 105: 331–343Abstract | Full Text | Full Text PDF | PubMed | Scopus (684)See all References1 in which subunit-specific AMPA receptor forms have different synaptic delivery mechanisms.In the hippocampus, most AMPA receptors are hetero-oligomers comprising GluR1–GluR2 or GluR2–GluR3 subunits. GluR1–GluR2 receptors are added to synapses during plasticity; this requires interactions between GluR1 and group I PDZ domain proteins. By contrast, GluR2–GluR3 receptors replace existing synaptic receptors continuously; this occurs only at synapses that already have AMPA receptors and requires GluR2 to interact with NSF and group II PDZ domain proteins.These novel studies suggest that there are two distinct mechanisms by which AMPA receptors can be delivered to synapses and provide evidence for how these mechanisms might contribute to important aspects of synaptic function. Shi et al. also suggest the existence of ‘slot’ proteins, which could serve as ‘placeholders’ that could be filled with nonsynaptic GluR2–GluR3 hetero-oligomers if synaptic GluR1–GluR2 or GluR2–GluR3 hetero-oligomers leave the synapse 1xSubunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Shi, S.-H. et al. Cell. 2001; 105: 331–343Abstract | Full Text | Full Text PDF | PubMed | Scopus (684)See all