Postsynaptic Kainate Receptor Recycling and Surface Expression Are Regulated by Metabotropic Autoreceptor Signalling

Maria Inmaculada Gonzalez, Jeremy M. Henley*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

12 Citations (Scopus)

Abstract

Kainate receptors (KARs) play fundamentally important roles in controlling synaptic function and regulating neuronal excitability. Postsynaptic KARs contribute to excitatory neurotransmission but the molecular mechanisms underlying their activity-dependent surface expression are not well understood. Strong activation of KARs in cultured hippocampal neurons leads to the downregulation of postsynaptic KARs via endocytosis and degradation. In contrast, low-level activation augments postsynaptic KAR surface expression. Here, we show that this increase in KARs is due to enhanced recycling via the recruitment of Rab11-dependent, transferrin-positive endosomes into spines. Dominant-negative Rab11 or the recycling inhibitor primaquine prevents the kainate-evoked increase in surface KARs. Moreover, we show that the increase in surface expression is mediated via a metabotropic KAR signalling pathway, which is blocked by the protein kinase C inhibitor chelerythrine, the calcium chelator BAPTA and the G-protein inhibitor pertussis toxin. Thus, we report a previously uncharacterized positive feedback system that increases postsynaptic KARs in response to low- or moderate-level agonist activation and can provide additional flexibility to synaptic regulation.

Original languageEnglish
Pages (from-to)810-822
Number of pages13
JournalTraffic
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2013

Keywords

  • G-protein-coupled receptors
  • glutamate receptor
  • kainate receptor
  • neuron
  • neuronal transmission
  • receptor recycling
  • synapse
  • LONG-TERM POTENTIATION
  • DENDRITIC SPINES
  • AMPA RECEPTORS
  • HIPPOCAMPAL-NEURONS
  • RAB GTPASES
  • BIDIRECTIONAL REGULATION
  • DIFFERENTIAL REGULATION
  • MEMBRANE
  • TRAFFICKING
  • ENDOSOMES

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