Skip to content

Now, let me review the GO-CAM model with ID 66b5638000002273 based on all the information I've gathered.

Review of GO-CAM Model 66b5638000002273

Model Information

  • Model ID: gomodel:66b5638000002273
  • Title: "GRIM1 activates GRID2 via GNAQ in Purkinje cells (Human)"
  • Taxon: Human (NCBITaxon:9606)
  • Status: Production

Overview of Model Content

This GO-CAM model describes a signaling pathway in human Purkinje cells where GRM1 (metabotropic glutamate receptor 1) activates GRID2 (glutamate receptor ionotropic delta-2) via GNAQ (G protein subunit alpha q) signaling. The model captures the molecular function, cellular location, and biological process of each component, as well as the causal relationships between them.

Model Components and Activities

1. GRM1 (UniProtKB:Q13255)

  • Molecular Function: GO:0099530 - G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential
  • Cellular Component: GO:0098839 - postsynaptic density membrane
  • Biological Process: GO:0007200 - phospholipase C-activating G protein-coupled receptor signaling pathway
  • Causal Relationship: Directly positively regulates GNAQ (RO:0002629)

2. GNAQ (UniProtKB:P50148)

  • Molecular Function: GO:0003925 - G protein activity
  • Cellular Component: GO:0099524 - postsynaptic cytosol
  • Biological Process: GO:0007200 - phospholipase C-activating G protein-coupled receptor signaling pathway
  • Causal Relationship: Directly positively regulates PLCB3 (RO:0002629)

3. PLCB3 (UniProtKB:Q01970)

  • Molecular Function: GO:0004435 - phosphatidylinositol phospholipase C activity
  • Cellular Component: GO:0099524 - postsynaptic cytosol
  • Biological Process: GO:0007200 - phospholipase C-activating G protein-coupled receptor signaling pathway
  • Outputs: CHEBI:17815 (1,2-diacyl-sn-glycerol) and CHEBI:203600 (1D-myo-inositol 1,4,5-trisphosphate)

4. PRKCG (UniProtKB:P05129)

  • Molecular Function: GO:0004698 - calcium,diacylglycerol-dependent serine/threonine kinase activity
  • Cellular Component: GO:0099524 - postsynaptic cytosol
  • Biological Process: GO:0007200 - phospholipase C-activating G protein-coupled receptor signaling pathway
  • Causal Relationship: Provides input for GRID2 (RO:0002407)

5. GRID2 (UniProtKB:O43424)

  • Molecular Function: GO:1904315 - transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
  • Cellular Component: GO:0098839 - postsynaptic density membrane
  • Biological Process: GO:0099538 - synaptic signaling via neuropeptide

Analysis of Causal Relationships

The model represents a signaling cascade where: 1. GRM1 activates GNAQ 2. GNAQ activates PLCB3 3. PLCB3 generates second messengers (IP3 and DAG) 4. PRKCG (activated by DAG and calcium) provides input for GRID2

This pathway accurately represents the canonical phospholipase C-activating G protein-coupled receptor signaling pathway, where GRM1 (mGlu1) activates GRID2 via the GNAQ-PLC-PKC pathway, as supported by the literature (particularly PMID:27276689).

Strengths of the Model

  1. Accurate molecular functions: Each protein is assigned appropriate molecular functions based on current knowledge.

  2. Correct subcellular localization: The subcellular locations are accurately represented, with GRM1 and GRID2 at the postsynaptic density membrane, and GNAQ, PLCB3, and PRKCG in the postsynaptic cytosol.

  3. Complete signaling pathway: The model captures the entire signaling cascade from receptor activation to the final effector.

  4. Evidence-based annotations: The annotations are supported by published literature, including experimental evidence from PMIDs 24357660, 27276689, 37991948, and 23115168.

  5. Correct causal relationships: The causal relationships between components are accurately represented using appropriate relationship ontology terms.

Areas for Improvement

  1. IP3 effect could be expanded: The model doesn't explicitly show the effect of IP3 on calcium release, which is part of the PKC activation mechanism. This could be included to make the model more complete.

  2. Molecular complex representation: The model does not represent any protein complexes. While this is appropriate based on the current evidence, if future research identifies specific complexes involved in this pathway, they could be included according to GO-CAM complex annotation guidelines.

  3. Feedback mechanisms: The model doesn't include any feedback mechanisms that might regulate this signaling pathway, which could be added if supported by evidence.

Consistency with GO-CAM Best Practices

The model follows GO-CAM best practices by:

  1. Using appropriate GO terms for molecular functions, cellular components, and biological processes
  2. Using correct relationship ontology terms for causal relationships
  3. Including evidence codes and references for annotations
  4. Maintaining consistency between molecular functions and their biological context

Biological Accuracy and Significance

This model accurately captures the current understanding of how mGluR1 (GRM1) activates GRID2 via the GNAQ-PLC-PKC signaling pathway in Purkinje cells. The literature supports that:

  1. GRM1 activation stimulates GNAQ (PMID:27276689)
  2. GNAQ activates PLCB3, leading to production of IP3 and DAG (PMID:37991948)
  3. DAG and calcium activate PRKCG (PMID:23115168)
  4. PRKCG contributes to GRID2 channel activation (PMIDs:24357660, 27276689)

The model is particularly significant because it explains the shared cerebellar motor phenotype observed in mutants of the mGluR1 and GluRĪ“2 signaling pathways, as indicated in PMID:23115168.

Conclusion

GO-CAM model 66b5638000002273 is a high-quality representation of the GRM1-GNAQ-PLCB3-PRKCG-GRID2 signaling pathway in human Purkinje cells. It accurately captures the molecular functions, cellular locations, biological processes, and causal relationships between components based on current evidence. The model provides valuable insights into the mechanism by which metabotropic glutamate receptor signaling regulates ionotropic glutamate receptor function in the cerebellum, which is critical for proper motor coordination.

The model could potentially be enhanced by including additional details about calcium signaling and feedback mechanisms, but as it stands, it represents a scientifically accurate and useful resource for understanding this important neuronal signaling pathway.