Auxiliary Subunits: Shepherding AMPA Receptors to the Plasma Membrane

Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated cation channels that mediate excitatory signal transmission in the central nervous system (CNS) of vertebrates. The members of the iGluR subfamily of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate most of the fast excitatory signal transmission, and their abundance in the postsynaptic membrane is a major determinant of the strength of excitatory synapses. Therefore, regulation of AMPAR trafficking to the postsynaptic membrane is an important constituent of mechanisms involved in learning and memory formation, such as long-term potentiation (LTP) and long-term depression (LTD). Auxiliary subunits play a critical role in the facilitation and regulation of AMPAR trafficking and function. The currently identified auxiliary subunits of AMPARs are transmembrane AMPA receptor regulatory proteins (TARPs), suppressor of lurcher (SOL), cornichon homologues (CNIHs), synapse differentiation-induced gene I (SynDIG I), cysteine-knot AMPAR modulating proteins 44 (CKAMP44), and germ cell-specific gene 1-like (GSG1L) protein. In this review we summarize our current knowledge of the modulatory influence exerted by these important but still underappreciated proteins.