title: The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity.
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.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jee Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Hey-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D002478:Cells, Cultured; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D018091:Receptors, AMPA / Q000032:analysis; D016019:Survival Analysis; D009435:Synaptic Transmission
chemical_list: D020690:GTPase-Activating Proteins; D009479:Neuropeptides; D018091:Receptors, AMPA; C112617:SynGAP protein p135