Small GTPase Rab17 regulates the surface expression of kainate receptors but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal neurons via dendritic trafficking of Syntaxin-4 protein

Yasunori Mori, Mitsunori Fukuda, Jeremy M Henley

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

9 Citations (Scopus)

Abstract

Glutamate receptors are fundamental for control synaptic transmission, synaptic plasticity, and neuronal excitability. However, many of the molecular mechanisms underlying their trafficking remain elusive. We previously demonstrated that the small GTPase Rab17 regulates dendritic trafficking in hippocampal neurons. Here, we investigated the role(s) of Rab17 in AMPA receptor (AMPAR) and kainate receptor (KAR) trafficking. Although Rab17 knockdown did not affect surface expression of the AMPAR subunit GluA1 under basal or chemically induced long term potentiation conditions, it significantly reduced surface expression of the KAR subunit GluK2. Rab17 co-localizes with Syntaxin-4 in the soma, dendritic shaft, the tips of developing hippocampal neurons, and in spines. Rab17 knockdown caused Syntaxin-4 redistribution away from dendrites and into axons in developing hippocampal neurons. Syntaxin-4 knockdown reduced GluK2 but had no effect on GluA1 surface expression. Moreover, overexpression of constitutively active Rab17 promoted dendritic surface expression of GluK2 by enhancing Syntaxin-4 translocation to dendrites. These data suggest that Rab17 mediates the dendritic trafficking of Syntaxin-4 to selectively regulate dendritic surface insertion of GluK2-containing KARs in rat hippocampal neurons.

Original languageEnglish
Pages (from-to)20773-87
Number of pages15
JournalJournal of Biological Chemistry
Volume289
Issue number30
DOIs
Publication statusPublished - 25 Jul 2014

Keywords

  • Animals
  • Dendrites
  • Gene Expression Regulation
  • HEK293 Cells
  • Hippocampus
  • Humans
  • Mice
  • Protein Transport
  • Qa-SNARE Proteins
  • Rats
  • Receptors, AMPA
  • Receptors, Kainic Acid
  • rab GTP-Binding Proteins

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