The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity

Jee Hae Kim, Hey Kyoung Lee, Kogo Takamiya, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptic GTPase-activating protein (SynGAP) is a neuronal RasGAP (Ras GTPase-activating protein) that is selectively expressed in brain and highly enriched at excitatory synapses, where it negatively regulates Ras activity and its downstream signaling pathways. To investigate the physiological role of SynGAP in the brain, we have generated mutant mice lacking the SynGAP protein. These mice exhibit postnatal lethality, indicating that SynGAP plays a critical role during neuronal development. In addition, cell biological experiments show that neuronal cultures from mutant mice have more synaptic AMPA receptor clusters, suggesting that SynGAP regulates glutamate receptor synaptic targeting. Moreover, electrophysiological studies demonstrated that heterozygous mutant mice have a specific defect in hippocampal long-term potentiation (LTP). These studies show that the regulation of synaptic Ras signaling by SynGAP is important for proper neuronal development and glutamate receptor trafficking and is critical for the induction of LTP.

Original languageEnglish (US)
Pages (from-to)1119-1124
Number of pages6
JournalJournal of Neuroscience
Volume23
Issue number4
DOIs
StatePublished - Feb 15 2003

Keywords

  • AMPA receptors
  • Excitatory synapses
  • Glutamate
  • Long-term depression
  • Long-term potentiation
  • NMDA receptors
  • Postsynaptic density
  • Ras signaling

ASJC Scopus subject areas

  • Neuroscience(all)

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