Ionotropic glutamate receptors (iGluRs) underlie rapid, excitatory synaptic signaling throughout the CNS. After years of intense research, our picture of iGluRs has evolved from imagining them companionless in the postsynaptic membrane to being the hub of dynamic supramolecular signaling complexes, interacting with an ever-expanding litany of other proteins that regulate their trafficking, scaffolding, stability, signaling and turnover. In particular, the discovery that transmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits of AMPA receptors, that are critical determinants of their trafficking, gating and pharmacology, has changed the way we think about iGluR function. Recently, a number of novel transmembrane proteins have been uncovered that may also serve as iGluR auxiliary proteins. Here we review pivotal developments in our understanding of the role of TARPs in AMPA receptor trafficking and gating, as well as an overview of how newly discovered transmembrane proteins expand our view of iGluR function in the CNS.
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