Regulation of AMPA receptors by transmembrane accessory proteins

Regulating the number and function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors located at the postsynaptic density is a key mechanism underlying synaptic strength and plasticity. Thus, an active area of investigation is the discovery of accessory proteins that regulate AMPA receptor trafficking and biophysical properties. One decade ago, pioneering studies identified the transmembrane protein stargazin as a critical regulator of synaptic targeting of AMPA receptors in cerebellar granule neurons. Stargazin-related family members called TARPs (transmembrane AMPA receptor regulatory proteins) are now recognized as essential auxiliary subunits for AMPA receptors that control both receptor trafficking and channel gating properties in a wide variety of neuronal cell types. Recent studies have identified a diverse array of additional accessory transmembrane proteins with distinct and overlapping functions compared with TARPs. Coupled with the wide variety of established cytoplasmic AMPA receptor accessory proteins, it is clear that AMPA receptor regulation encompasses a previously unrecognized diversity of molecular mechanisms.