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ARF1 regulates pH-dependent COP functions in the early endocytic pathway
1Department of Biochemistry, Sciences II, University of Geneva, 30 quai E. Ansermet, CH-1211 Geneva 4, Switzerland.
The Journal of Biological Chemistry
|March 14, 2000
Summary
Small GTP-binding protein ARF1 regulates COP protein function in endocytic pathway transport. ARF1 recruitment to endosomes depends on acidic pH, controlling COP association and biogenesis of late endosome intermediates.
Area of Science:
- Cell Biology
- Molecular Biology
- Endocytosis
Background:
- COP proteins are involved in membrane transport in both biosynthetic and endocytic pathways.
- Endosomal COP association is dependent on acidic endosomal pH, unlike biosynthetic COPs.
Purpose of the Study:
- To identify cytosolic factors regulating endosomal COP recruitment and function.
- To elucidate the role of ARF1 in the endocytic pathway and its regulation by pH.
Main Methods:
- In vitro biogenesis assays.
- Identification of cytosolic factors using biochemical approaches.
- Analysis of ARF1 membrane association and its regulation by pH.
Main Results:
- The small GTP-binding protein ARF1 was identified as a key cytosolic factor for endosomal COP recruitment and in vitro biogenesis of late endosome intermediates.
- ARF1 does not function via activation of endosomal phospholipase D.
- ARF1 membrane association is regulated by endosomal pH, which in turn controls pH-dependent endosomal COP association.
Conclusions:
- ARF1 is essential for regulating COP functions within the endocytic pathway.
- ARF1 acts as a cytosolic component of a transmembrane pH-sensing mechanism, linking endosomal pH to COP-mediated transport.
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