The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity.
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.
Kim
Jee Hae
JH
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Lee
Hey-Kyoung
HK
Takamiya
Kogo
K
Huganir
Richard L
RL
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
D020690:GTPase-Activating Proteins; D009479:Neuropeptides; D018091:Receptors, AMPA; C112617:SynGAP protein p135