Auxiliary subunits provide new insights into regulation of AMPA receptor trafficking.

Glutamate is a major excitatory neurotransmitter in the vertebrate brain. Among the ionotropic glutamate receptors, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors are the major receptors mediating excitatory fast synaptic transmission. AMPA receptors are also responsible for modifying synaptic strength through the regulation of their numbers at synapses. Their high regulatability, therefore, could contribute to the mechanisms of synaptic plasticity. The mechanisms regulating AMPA receptor trafficking have evoked great interest through the decades. Recent studies show that in the brain, AMPA receptors make complexes with transmembrane AMPA regulatory proteins (TARPs), which serve as auxiliary subunits. TARPs are required for AMPA receptor function and trafficking. After the initial discovery of TARPs, several other AMPA receptor auxiliary subunits were identified: CNIH-2, CNIH-3, CKAMP44, SynDIG1, SOL-1, SOL-2 and GSG-1L. This review discusses progress in identifying the role of auxiliary subunits in AMPA receptor trafficking.