Regulation of AMPA receptor trafficking and exit from the endoplasmic reticulum

    loading  Checking for direct PDF access through Ovid


A fundamental property of the brain is its ability to modify its function in response to its own activity. This ability for self-modification depends to a large extent on synaptic plasticity. It is now appreciated that for excitatory synapses, a significant part of synaptic plasticity depends upon changes in the post synaptic response to glutamate released from nerve terminals. Modification of the post synaptic response depends, in turn, on changes in the abundances of AMPA receptors in the post synaptic membrane. In this review, we consider mechanisms of trafficking of AMPA receptors to and from synapses that take place in the early trafficking stages, starting in the endoplasmic reticulum (ER) and continuing into the secretory pathway. We consider mechanisms of AMPA receptor assembly in the ER, highlighting the role of protein synthesis and the selective properties of specific AMPA receptor subunits, as well as regulation of ER exit, including the roles of chaperones and accessory proteins and the incorporation of AMPA receptors into COPII vesicles. We consider these processes in the context of the mechanism of mGluR LTD and discuss a compelling role for the dendritic ER membrane that is found proximal to synapses. The review illustrates the important, yet little studied, contribution of the early stages of AMPA receptor trafficking to synaptic plasticity.HighlightsAMPA receptor trafficking in the early stages of the secretory pathway contributes to synaptic plasticityDifferences in AMPA receptor subunit localization and dynamics in the ER contribute to different trafficking patterns.In the ER, protein synthesis, subunit assembly and receptor incorporation into COPII vesicles regulate receptor trafficking.Special features of the dendritic ER proximal to synapses may facilitate receptor transport to synapsesThe mechanism of mGluR LTD may utilize regulation of receptor trafficking in the early secretory pathway

    loading  Loading Related Articles