PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression

Chi Bun Chan, Yongjun Chen, Xia Liu, Xiaoling Tang, Chi Wai Lee, Lin Mei, Keqiang Ye

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

AMPAR (α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an ion channel involved in the formation of synaptic plasticity. However, the molecular mechanism that couples plasticity stimuli to the trafficking of postsynaptic AMPAR remains poorly understood. Here, we show that PIKE (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by promoting GluA2/GRIP1 association. PIKE-L directly interacts with both GluA2 and GRIP1 and forms a tertiary complex upon glycine-induced NMDA receptor activation. PIKE-L is also essential for glycine-induced GluA2-associated PI3K activation. Genetic ablation of PIKE (PIKE -/-) in neurons suppresses GluA2-associated PI3K activation, therefore inhibiting the subsequent surface expression of GluA2 and the formation of long-term potentiation. Our findings suggest that PIKE-L is a critical factor in controlling synaptic AMPAR insertion.

Original languageEnglish (US)
Pages (from-to)4274-4286
Number of pages13
JournalEMBO Journal
Volume30
Issue number20
DOIs
StatePublished - Oct 19 2011

Keywords

  • GRIP1
  • GluA2
  • LTP
  • PI3K
  • PIKE

ASJC Scopus subject areas

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

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  • Cite this

    Chan, C. B., Chen, Y., Liu, X., Tang, X., Lee, C. W., Mei, L., & Ye, K. (2011). PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression. EMBO Journal, 30(20), 4274-4286. https://doi.org/10.1038/emboj.2011.281