Learning and memory are thought to be supported by experience-dependent neuronal plasticity; found mechanism of postsynaptic localization of AMPA-type glutamate receptors & their regulation

Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation. Olivia R. Buonarati et al. Sci. Signal.  Jan 01 2019:Vol. 12, Issue 562, eaar6889. http://stke.sciencemag.org/content/12/562/eaar6889

Gloss: Learning and memory are thought to be supported by experience-dependent neuronal plasticity, which on a cellular level is expressed as long-term changes (such as potentiation or depression) of synaptic responses. Glutamate-gated ion channels known as AMPA receptors mediate basal neurotransmission. Their postsynaptic functional availability can be selectively modulated in correlation with a given stimulus. This review discusses the molecular basis of AMPA receptor trafficking to and anchoring at excitatory postsynaptic sites and their regulation by protein kinases.

Abstract: l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited to and anchored at postsynaptic sites. Emerging findings continue to shed new light on molecular mechanisms that mediate AMPAR postsynaptic trafficking and localization. Accordingly, unconventional secretory trafficking of AMPARs occurs in dendrites, from the endoplasmic reticulum (ER) through the ER-Golgi intermediary compartment directly to recycling endosomes, independent of the Golgi apparatus. Upon exocytosis, AMPARs diffuse in the plasma membrane to reach the postsynaptic site, where they are trapped to contribute to transmission. This trapping occurs through a combination of both intracellular interactions, such as TARP (transmembrane AMPAR regulatory protein) binding to α-actinin–stabilized PSD-95, and extracellular interactions through the receptor amino-terminal domain. These anchoring mechanisms may facilitate precise receptor positioning with respect to glutamate release sites to enable efficient synaptic transmission.