The ins and outs of glutamate receptor trafficking during synaptic plasticity

抄録

Glutamate, the major excitatory neurotransmitter in the brain, acts primarily on two types of ionotropic receptors, AMPA receptors and NMDA receptors. Work over the past decade indicates that the number of synaptic AMPA receptors is tightly regulated and may serve as a mechanism for information storage. Recent studies show that stargazin, the mutated protein in the ataxic and epileptic mouse stargazer, is necessary for the expression of surface AMPA receptors in cerebellar granule cells. Stargazin is a small tetraspanning membrae protein and is a member of a family of proteins referred to as transmembrane AMPAR regulatory proteins (TARPs). These proteins are differentially expressed throughout the brain. TARPs control AMPA receptor trafficking through the endoplasmic reticulum and are important for the maturation and proper folding of AMPARs. They are necessary for the delivery of AMPA receptors to the cell surface, as well as to the synapse. Finally TARPs control the gating of synaptic receptors. The role of TARPs is analogous to non-pore forming auxiliary subunits of voltage gated ion channels. Thus TARPs provide the first example of auxiliary subunits of ionotropic receptors. In this talk I will review the pivotal role that TARPs play in the life history of an AMPA receptor. [J Physiol Sci. 2006;56 Suppl:S2]