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Based on my review of the GO-CAM model gomodel:62f58d8800001119 titled "Insulin receptor recycling (Mouse)", here's my assessment:

GO-CAM Review: Insulin Receptor Recycling (Mouse) gomodel:62f58d8800001119

Summary

This model represents the process of insulin receptor recycling in mouse (NCBITaxon:10090), highlighting the molecular mechanisms involved in insulin receptor endocytosis, processing, and recycling. The model is in production status and focuses on several key proteins and complexes involved in this pathway.

Model Structure and Content

The model includes these key activities: 1. Protein binding by SORL1 (MGI:MGI:1202296) 2. Endopeptidase activities by CTSD (MGI:MGI:88562) and IDE (MGI:MGI:96412) 3. Protein tyrosine phosphatase activities by PTPN1 (MGI:MGI:97805) and PTPN2 (MGI:MGI:97806) 4. Proton transmembrane transport by the V-type ATPase complex (GO:0033176) 5. ATP hydrolysis by the V1 domain of the V-type ATPase complex (GO:0033180) 6. Molecular function activator activity by ATP6AP1 (MGI:MGI:109629)

Strengths of the Model

  1. Well-supported evidence: The model incorporates multiple evidence codes and literature references, primarily from PMID:27322061 which extensively describes the role of SORLA (SORL1) in insulin receptor trafficking and signaling.

  2. Appropriate cellular localization: The activities are appropriately localized to relevant cellular components, with key processes occurring in the endosome lumen (GO:0031904) and endosome membrane (GO:0010008).

  3. Proper complex annotation: The V-type ATPase complex is correctly represented following GO-CAM guidelines for complexes. The activities are enabled by the appropriate complex components (V0 domain GO:0033179 and V1 domain GO:0033180) with their subunits properly listed.

  4. Causal connections: The model effectively shows the causal relationships between activities using appropriate relationship predicates.

Areas for Improvement

  1. Missing insulin binding: The model does not explicitly represent the initial binding of insulin to its receptor, which is the trigger for the receptor internalization process.

  2. Incomplete representation of insulin signaling: While the model focuses on insulin receptor recycling, it could benefit from connections to downstream insulin signaling pathways that are affected by changes in receptor recycling rates.

  3. Limited molecular details of sorting: The molecular sorting mechanism of SORL1 could be more explicitly represented, showing how it interacts with the insulin receptor in the sorting process.

Consistency with Literature

The model is highly consistent with the referenced literature, particularly PMID:27322061, which describes how SORLA (SORL1) facilitates insulin receptor recycling by redirecting internalized receptor molecules from endosomes to the plasma membrane. The paper establishes that SORLA: - Interacts directly with the insulin receptor - Increases insulin receptor surface expression - Promotes insulin signaling in adipocytes - Prevents lysosomal degradation of the receptor - Enhances receptor recycling to the cell surface

The model captures these key aspects of the mechanism described in the literature.

Biological Accuracy

The biological content of the model is accurate and consistent with current understanding of insulin receptor trafficking. The inclusion of the V-type ATPase in endosomal acidification is appropriate, as acidification of endosomes is crucial for receptor sorting decisions.

The model correctly represents: - The role of protein tyrosine phosphatases in insulin receptor signaling - The involvement of endopeptidases in insulin processing - The role of the V-type ATPase in creating the acidic environment needed for proper endosomal function - The importance of SORL1 in the receptor recycling pathway

Technical Assessment

  1. Appropriate use of GO terms: The molecular functions, cellular components, and biological processes are correctly represented using appropriate GO terms.

  2. Correct evidence codes: The model uses correct evidence codes (ECO terms) with appropriate references.

  3. Appropriate causal relationships: The causal relationships use correct relationship predicates (RO terms).

Recommendations for Improvement

  1. Add insulin binding: Include the initial insulin binding event to provide a complete picture of the pathway.

  2. Expand on downstream effects: Consider adding connections to show how altered receptor recycling affects insulin signaling outcomes.

  3. Include additional sorting components: The model could benefit from including other known components of the endosomal sorting machinery that may interact with SORL1.

  4. Add molecular details of SORL1-insulin receptor interaction: Based on PMID:27322061, include more details about how SORL1 interacts with the insulin receptor and redirects it from the degradative to the recycling pathway.

Conclusion

The GO-CAM model gomodel:62f58d8800001119 is a well-constructed representation of insulin receptor recycling in mouse. It is consistent with the literature and generally follows GO-CAM best practices for representing molecular activities, cellular components, and causal relationships. With the suggested improvements, the model could provide an even more comprehensive view of this important cellular process.