| Annotated protein: | Ras-specific guanine nucleotide-releasing factor 1 (Ras-GRF1) (Guanine nucleotide-releasing protein) (GNRP) (P140 Ras-GRF). Gene symbol: RASGRF1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P28818 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ RASGRF1 |
| Ontology domain: | Cellular Component |
| SynGO term: | postsynapse (GO:0098794) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Krapivinsky G, et al. "The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1" Neuron. 2003 Nov 13;40(4):775-84 PMID:14622581 |
| Figure(s): | Figure 1, 2, 3, 5 |
| Annotation description: | Figure 1, 2: NR2B (GRIN2B) and RasGRF1 (aka. GRF1, GNRP, CDC25) interact in vitro and in vivo. "Thus, truncation of the RasGRF1-specific sequence from either the C or N terminus resulted in loss of binding, suggesting that several separated protein segments may be responsible for specific interactions. Therefore, the RasGRF1 domain interacting with NR2B is localized between amino acids 714-913 of RasGRF1. The peptide encoding this region of RasGRF1 was designated as the RasGRF1-BD and used in subsequent experiments." Figure 3: Disruption of NR2B-RasGRF1 interaction abrogates NMDAR-dependent ERK1,2 activation. "Thus, expression of the dominant-negative form of RasGRF1, the complete BDs (but not overlapping peptides encoding only portions of the binding domains), effectively inhibited the NMDAR-dependent activation of ERK. These data support the hypothesis that a direct link between NR2B and RasGRF1 is critical for NMDAR-specific ERK activation." Figure 5: Blocking peptides RasGRF1-BD and NR2B-BD did not change the localization or density of NR2B or PSD95. Thus further supports the model proposed by authors where RasGRF1 directly interacts with NR2B at the postsynaptic membrane in order to activate ERK. authors summarise; "Suppression of NMDA-dependent ERK activation by the dominant-negative form of RasGRF1 suggests that RasGRF1 is a crucial intermediate between the NMDAR and ERK activation. The interaction between NR2B and RasGRF1, and our demonstration that disruption of this interaction attenuated NMDA-dependent ERK activation, strongly suggests that the NR2B subunit directly links the NMDAR to ERK activation. This finding, together with fact that both ERK (Adams and Sweatt, 2002) and RasGRF1 (Giese et al., 2001) are important for hippocampal-dependent memory, suggests that the NMDAR-RasGRF1-ERK signaling chain is integral to hippocampal memory formation." |
| Evidence tracking, Biological System: | Non-neuronal tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Antagonist / agonist Antibody (detection) |
| Evidence tracking, Experiment Assay: | IP + WB/MSMS Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 5460 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |