| Annotated protein: | GRIP1-associated protein 1 (GRASP-1) (HCMV-interacting protein) [Cleaved into: GRASP-1 C-terminal chain (30kDa C-terminus form)]. Gene symbol: GRIPAP1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8VD04 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ GRIPAP1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane (GO:0099152) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Chiu SL, et al. "GRASP1 Regulates Synaptic Plasticity and Learning through Endosomal Recycling of AMPA Receptors" Neuron. 2017 Mar 22;93(6):1405-1419.e8 PMID:28285821 |
| Figure(s): | Fig. 1, Fig. 2, Fig. 3, Fig.5, 6 |
| Annotation description: | Fig. 1, the figure shows that Grasp1 (GRIP-associated protein 1, GRIPAP1) KO Mice Have Reduced AMPA mEPSC frequency and dendritic spines. Literal: "However, mEPSC frequency in KO mice was significantly reduced compared to WT littermates (Figures 1A and 1C), suggesting that GRASP1 mediates neuronal connectivity and/or presynaptic glutamate release. To test whether the reduced mEPSC frequency reflects a decrease in glutamatergic synapse number, we crossed Grasp1 mice with Thy1-GFP transgenic mice to sparsely label CA1 neurons with a GFP-fill (Figure 1E). We found that the glutamatergic synapse density, quantified as the number of spines on secondary dendrites, was significantly lower in juvenile KO than WT littermates (Figures 1E and 1F), suggesting that GRASP1 regulates neuronal connectivity in the developing hippocampus." Fig. 2, Grasp1 KO Mice show impaired NMDAR-dependent LTP but normal LTD and presynaptic function because GRASP1 is required for the appropriate delivery of synaptic AMPARs. Literal: "LTP induction resulted in an initially less potentiated field excitatory postsynaptic potential (fEPSP) and remained reduced for at least 1 hr in Grasp1 KO mice (Figures 2A-2C). Since this form of LTP results from an increase in postsynaptic AMPARs (Huganir and Nicoll, 2013), these results suggest that GRASP1 is required for the appropriate delivery of synaptic AMPARs in response to TBS. On the other hand, NMDAR-mediated LTD was not different between KO and WT mice (Figures 2D and 2E), suggesting a specific role of GRASP1 in activity-dependent incorporation, but not removal, of synaptic AMPARs. We further tested whether GRASP1 regulates presynaptic function by comparing paired-pulse ratios (PPRs), a standard approach to assess neurotransmitter release probability. Grasp1 KO mice showed comparable PPRs in a wide range of interstimulus intervals, suggesting that GRASP1 does not regulate presynaptic vesicle release (Figure 2F). Together with the observation that Grasp1 KO mice had fewer spines, we concluded that the attenuated mEPSC frequency reflects primarily a reduction in glutamatergic inputs onto hippocampal CA1 neurons." Fig. 3, Grasp1 KO mice show impaired learning-induced synaptic AMPAR incorporation. Literal: "To test whether GRASP1 is required for learning-induced synaptic AMPAR delivery, we isolated the postsynaptic density (PSD) fraction, highly enriched in synaptic proteins, from the dorsal hippocampus of adult Grasp1 mice 30 min following IA training. Consistent with previous findings, we found that in WT animals, IA training increased the levels of GluA1, 2, and 3 AMPAR subunits compared to littermates that did not receive a foot shock (Figures 3F and 3G). The learning-induced increase in synaptic glutamate receptors is AMPAR specific because we did not detect changes in the NMDAR subunit GluN1 or the metabotropic glutamate receptor 5 (mGluR5). Remarkably, this learning-induced increase in AMPAR is completely abolished in KO mice (Figures 3F and 3G). AMPARs in the post-nuclear supernatant (S1) fraction remain comparable regardless of the genotype and IA training, indicating that GRASP1 is specifically required for synaptic delivery of AMPARs during IA learning (Figures 3H and 3I). Taken together, these data demonstrate a critical role for GRASP1 in spatial (MWM) and associative (IA) learning and memory, likely via regulation of activity-dependent AMPAR trafficking and synaptic potentiation." 9/11/2017 Pim - GRASP1 KO --> Literal: "Our finding that Grasp1 KO mice have impaired LTP but normal mEPSC amplitude suggests that GRASP1 is selectively required for activity-dependent AMPAR trafficking and synaptic strengthening" - GRASP1 ID mutant --> Literal: "These data further support our argument that the reduction in sGluA2 following AMPA stimulation in ID mutant-replaced neurons (Figures 5D and 5F) is a result of recycling effect, but not AMPAR degradation." - term: 'regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane (GO:0099152)' was selected based on these conclusions |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) RNAi / shRNA Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Field recordings Western blot Biochemical fractionation (generic) |
| Annotator(s): | Chiara Verpelli (ORCID:0000-0003-2949-9725) Carlo Sala (ORCID:0000-0003-0662-9523) |
| Lab: | CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy |
| SynGO annotation ID: | 1744 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |