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

First Author  Kim JH Year  2003
Journal  J Neurosci Volume  23
Issue  4 Pages  1119-24
PubMed ID  12598599 Mgi Jnum  J:97391
Mgi Id  MGI:3575363 Doi  10.1523/JNEUROSCI.23-04-01119.2003
Citation  Kim JH, et al. (2003) The role of synaptic GTPase-activating protein in neuronal development and synaptic plasticity. J Neurosci 23(4):1119-24
abstractText  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.
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