Assembly, Secretory Pathway Trafficking, and Surface Delivery of Kainate Receptors Is Regulated by Neuronal Activity

Ashley J. Evans, Sonam Gurung, Kevin A. Wilkinson, David J. Stephens, Jeremy M. Henley

Research output: Contribution to journalArticle (Academic Journal)peer-review

35 Citations (Scopus)
382 Downloads (Pure)

Abstract

Summary Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity. We show that the delivery of de novo kainate receptors is differentially regulated by modulation of GluK2 Q/R editing, PKC phosphorylation, and PDZ ligand interactions. These findings reveal that, in addition to short-term regulation of iGluRs by recycling/endocytosis and long-term modulation by altered transcription/translation, the trafficking of iGluRs through the secretory pathway is under tight activity-dependent control to determine the numbers and properties of surface-expressed iGluRs.
Original languageEnglish
Pages (from-to)2613-2626
Number of pages14
JournalCell Reports
Volume19
Issue number12
Early online date20 Jun 2017
DOIs
Publication statusPublished - 20 Jun 2017

Keywords

  • kainate receptor
  • retention using selective hooks
  • RUSH
  • secretory pathway
  • ER exit sites
  • Golgi outposts
  • AMPA receptors
  • scaling
  • Q/R editing
  • ADAR2
  • PDZ ligand

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