Association of the small GTPase Rheb with the NMDA receptor subunit NR3A

Nikolaus J. Sucher, Eric Yu, Shing Fai Chan, Mitra Miri, Benjamin J. Lee, Bo Xiao, Paul F. Worley, Frances E. Jensen

Research output: Contribution to journalArticle

Abstract

The NMDAR subunit NR3A is most highly expressed during the second postnatal week, when synaptogenesis reaches peak levels. Genetic ablation or overexpression of the NR3A subunit negatively interferes with the maturation of cortical synapses and leads to changes in the shape and number of dendritic spines, the density of which is increased in NR3A knock-out mice and decreased in NR3A-overexpressing transgenic mice. Alterations in spine density have been linked to dysregulation of mTOR signaling and synaptic protein translation. Using a yeast two-hybrid system, we identified the mTOR-activating GTPase Rheb as an interacting protein of the NMDAR subunit NR3A. We confirmed the interaction in mammalian cells by expressing recombinant Rheb and NR3A and showed that Rheb and NR3A could be co-immunoprecipitated from synaptic plasma membranes from the developing rat brain. These data suggest that NR3A sequesters synaptic Rheb and might thus function as a break of the mTOR-dependent synaptic translation of protein.

Original languageEnglish (US)
Pages (from-to)203-209
Number of pages7
JournalNeuroSignals
Volume18
Issue number4
DOIs
StatePublished - Mar 2011

Keywords

  • NMDA receptor
  • Plasticity
  • Rheb
  • Synapse
  • Translation
  • mTOR

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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  • Cite this

    Sucher, N. J., Yu, E., Chan, S. F., Miri, M., Lee, B. J., Xiao, B., Worley, P. F., & Jensen, F. E. (2011). Association of the small GTPase Rheb with the NMDA receptor subunit NR3A. NeuroSignals, 18(4), 203-209. https://doi.org/10.1159/000322206