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A Commander-independent function of COMMD3 in endosomal trafficking
Galen T Squiers1, Chun Wan1, James Gorder1
1Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Biorxiv : the Preprint Server for Biology
|January 7, 2025
Summary
The Commander complex is vital for endosomal recycling, but a subunit, COMMD3, surprisingly functions independently. COMMD3 regulates cargo recycling by stabilizing ARF1, revealing novel roles for complex subunits.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Complexes
Background:
- Endosomal recycling is crucial for preventing lysosomal degradation of proteins.
- The 16-subunit Commander complex is a key regulator of endosomal recycling.
- The precise molecular mechanisms of the Commander complex are not fully understood.
Purpose of the Study:
- To genetically dissect the Commander complex and elucidate its molecular mechanism.
- To investigate potential Commander-independent functions of its subunits.
- To understand the role of COMMD3 in endosomal recycling.
Main Methods:
- Unbiased genetic screens were employed to dissect the Commander complex.
- Comparative targeted mutations were used to analyze subunit functions.
- The interaction between COMMD3 and ARF1 was investigated.
Main Results:
- COMMD3, a Commander subunit, exhibits a Commander-independent function in endosomal recycling.
- COMMD3 regulates a distinct subset of cargo proteins.
- The N-terminal domain of COMMD3 binds and stabilizes ARF1, a GTPase involved in recycling.
- Mutations disrupting the COMMD3-ARF1 interaction impair cargo recycling.
Conclusions:
- Commander subunits can possess functions independent of the holo-complex.
- COMMD3's interaction with ARF1 is critical for its independent role in endosomal recycling.
- This discovery suggests other membrane trafficking complex components may also have extracomplex functions.
Keywords:
CommanderGolgiRetromerendocytic pathwayendosomal recyclingendosomemembrane traffickingplasma membraneMore Related Videos
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