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PMID:9620694
| Citation |
Chen, HJ, Rojas-Soto, M, Oguni, A and Kennedy, MB (1998) A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20:895-904 |
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| Abstract |
Ca2+ influx through N-methyl-D-aspartate- (NMDA-) type glutamate receptors plays a critical role in synaptic plasticity in the brain. One of the proteins activated by the increase in Ca2+ is CaM kinase II (CaMKII). Here, we report a novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major component of the postsynaptic density, a complex of proteins associated with synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses in hippocampal neurons where it binds to and closely colocalizes with the scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors. |
| Links | |
| Keywords |
Animals; Brain/enzymology; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Carrier Proteins/antagonists & inhibitors; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cells, Cultured; Enzyme Inhibitors/metabolism; GTP Phosphohydrolases/metabolism; GTPase-Activating Proteins; Glutamic Acid/physiology; Hippocampus/cytology; Molecular Sequence Data; Neurons/chemistry; Neurons/cytology; Neurons/enzymology; Neuropeptides/antagonists & inhibitors; Neuropeptides/genetics; Neuropeptides/metabolism; Phosphorylation; RNA, Messenger/analysis; Rats; Receptors, N-Methyl-D-Aspartate/analysis; Receptors, N-Methyl-D-Aspartate/metabolism; Sequence Homology, Amino Acid; Substrate Specificity; Synapses/chemistry; Synapses/enzymology; ras Proteins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0045202: synapse |
ECO:0000314: |
C |
Figure 5, C Two yeast two-hybrid bait constructs were tested for interaction with full-length PSD-95 as described in Experimental Procedures. The +QTRV construct interacts strongly, whereas the −QTRV construct does not. |
complete | ||||
|
part_of |
GO:0045202: synapse |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
See also
References
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