title: SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family.
abstract: The PSD-95/SAP90 family of proteins has recently been implicated in the organization of synaptic structure. Here, we describe the isolation of a novel Ras-GTPase activating protein, SynGAP, that interacts with the PDZ domains of PSD-95 and SAP102 in vitro and in vivo. SynGAP is selectively expressed in brain and is highly enriched at excitatory synapses, where it is present in a large macromolecular complex with PSD-95 and the NMDA receptor. SynGAP stimulates the GTPase activity of Ras, suggesting that it negatively regulates Ras activity at excitatory synapses. Ras signaling at the postsynaptic membrane may be involved in the modulation of excitatory synaptic transmission by NMDA receptors and neurotrophins. These results indicate that SynGAP may play an important role in the modulation of synaptic plasticity.
authors.affiliation: Department of Neuroscience, Howard Huges Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Liao
authors.forename: L F
authors.initials: LF
authors.lastname: Lau
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D000076122:Disks Large Homolog 4 Protein; D020690:GTPase-Activating Proteins; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074407:SAP90-PSD95 Associated Proteins; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D014162:Transfection; D020703:ras GTPase-Activating Proteins
chemical_list: D002352:Carrier Proteins; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D000074407:SAP90-PSD95 Associated Proteins; C484739:SYNGAP1 protein, human; C112202:Syngap1 protein, rat; C033652:postsynaptic density proteins; D020703:ras GTPase-Activating Proteins