Rapid and bi-directional regulation of AMPA receptor phosphorylation and trafficking by JNK

Gareth M. Thomas, Da Ting Lin, Mutsuo Nuriya, Richard L. Huganir

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Jun N-terminal kinases (JNKs) are implicated in various neuropathological conditions. However, physiological roles for JNKs in neurons remain largely unknown, despite the high expression level of JNKs in brain. Here, using bioinformatic and biochemical approaches, we identify the AMPA receptor GluR2L and GluR4 subunits as novel physiological JNK substrates in vitro, in heterologous cells and in neurons. Consistent with this finding, GluR2L and GluR4 associate with specific JNK signaling components in the brain. Moreover, the modulation of the novel JNK sites in GluR2L and GluR4 is dynamic and bi-directional, such that phosphorylation and de-phosphorylation are triggered within minutes following decreases and increases in neuronal activity, respectively. Using live-imaging techniques to address the functional consequence of these activity-dependent changes we demonstrate that the novel JNK site in GluR2L controls reinsertion of internalized GluR2L back to the cell surface following NMDA treatment, without affecting basal GluR2L trafficking. Taken together, our results demonstrate that JNK directly regulates AMPA-R trafficking following changes in neuronal activity in a rapid and bi-directional manner.

Original languageEnglish
Pages (from-to)361-372
Number of pages12
JournalEMBO Journal
Volume27
Issue number2
DOIs
Publication statusPublished - 2008 Jan 23

Keywords

  • LTD
  • LTP
  • MAPK
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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