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Based on my review, I'll now provide a detailed assessment of GO-CAM model 65d7e4ac00001800 "RUFY1 mediates early endosome to Golgi transport. (Human)".

GO-CAM Review: gomodel:65d7e4ac00001800

Summary

This model represents the role of RUFY1 (Q96T51) as a protein-macromolecule adaptor that mediates early endosome to Golgi transport via endosomal fusion, with involvement of Rab GTPases RAB4B (P61018) and RAB14 (P61106), along with ARL8B (Q9NVJ2). The model depicts the molecular functions of these proteins and causal relationships where ARL8B impacts RUFY1 function, which in turn affects RAB4B and RAB14 activities.

Strengths

  1. Accurate representation of molecular functions: The model correctly assigns GTPase activity (GO:0003924) to RAB4B, RAB14, and ARL8B, which aligns with their known roles as small GTPases.

  2. Appropriate cellular locations: All activities are correctly shown to occur in the early endosome membrane (GO:0031901).

  3. Correct biological process assignment: The model appropriately associates ARL8B with protein localization to early endosome (GO:1902946) and RAB4B/RAB14/RUFY1 with both endosomal vesicle fusion (GO:0034058) and early endosome to Golgi transport (GO:0034498).

  4. Causal relationships: The model accurately depicts the relationship where ARL8B directly positively regulates RUFY1, which then directly positively regulates both RAB GTPases, reflecting the finding from the literature that ARL8B promotes RUFY1 endosomal localization and function.

  5. Evidence and citations: All activities and relationships are supported by appropriate experimental evidence (ECO:0000314 - direct assay evidence) and cited research papers.

Areas for Improvement

  1. Missing protein complex representation: The model doesn't explicitly represent the RUFY1-RAB14-RAB4B complex that forms on early endosomes. According to the "How to annotate complexes in GO-CAM" guide, if the activity is shared by several proteins or if the precise subunit carrying an activity isn't known, a complex representation might be appropriate.

  2. Incomplete representation of dynein interaction: The recent literature (PMID:36282215) shows that RUFY1 interacts with the dynein-dynactin complex, which is important for the retrograde transport function. This interaction and its role in CI-M6PR trafficking could be added to the model.

  3. Missing molecular function detail: While RUFY1's protein-macromolecule adaptor activity (GO:0030674) is correctly captured, its RUN domain-mediated interaction with ARL8B could be more explicitly represented.

  4. Incomplete representation of transport process: The model shows endosomal vesicle fusion but doesn't fully capture the complete process of cargo movement from early endosomes to the TGN.

Recommendations

  1. Add complex representation: Consider adding a representation of the RUFY1-RAB14-RAB4B complex that forms on early endosomes, especially since the papers indicate this is a functional unit for endosomal tethering and fusion.

  2. Include dynein interaction: Add the interaction between RUFY1 and the dynein-dynactin complex, which is important for retrograde transport. This would provide a more complete picture of how RUFY1 mediates transport.

  3. Expand molecular function details: Add more specific molecular function annotations for RUFY1, particularly related to its RUN domain interaction with ARL8B and its coiled-coil domains' interaction with dynein.

  4. Add cargo representation: Consider adding a representation of CI-M6PR (cation-independent mannose-6-phosphate receptor) as cargo that gets trafficked in this process, as this would make the model more complete and biologically relevant.

  5. Add more biological context: Include annotations about the consequence of this transport process - the sorting of lysosomal hydrolases - to provide a more comprehensive view of the biological significance.

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents the current understanding of RUFY1's role in mediating early endosome to Golgi transport with the involvement of RAB4B, RAB14, and ARL8B. The model captures the key molecular functions, cellular locations, biological processes, and causal relationships supported by the literature. With the suggested improvements, particularly regarding complex representation and the inclusion of dynein interaction, the model would provide an even more comprehensive and accurate representation of this biological process.

The model is consistent with GO-CAM best practices and represents the biological content in alignment with the published literature. It is parsimonious yet informative, focusing on the essential components and relationships in this transport pathway.