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ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation
Stella Y Lee1, Jia-Shu Yang, Wanjin Hong
1Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115.
The Journal of Cell Biology
|January 20, 2005
Summary
GTPase-activating protein (GAP) directly promotes cargo binding to coatomer and is critical for COPI vesicle formation, challenging previous models of COPI transport and cargo sorting.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Transport
Background:
- Coat protein I (COPI) vesicles mediate retrograde transport within the Golgi apparatus.
- ADP ribosylation factor 1 (ARF1) is a key regulator of COPI vesicle formation and function.
- The precise roles of ARF1 and its regulators in cargo sorting remain incompletely understood.
Purpose of the Study:
- To investigate the direct role of GTPase-activating protein (GAP) in COPI-mediated cargo sorting.
- To elucidate the function of GAP catalytic activity in COPI vesicle formation.
- To re-evaluate the interplay between cargo sorting and vesicle formation in COPI transport.
Main Methods:
- Biochemical assays to assess protein-protein interactions.
- In vitro assays to study vesicle budding from Golgi membranes.
- Analysis of ARF1 and GAP function in COPI transport.
Main Results:
- GTPase-activating protein (GAP), not ADP ribosylation factor 1 (ARF1), directly promotes cargo protein binding to coatomer.
- Activated ARF1 selectively binds to SNARE cargo proteins, potentially stabilizing ARF1 on Golgi membranes.
- GAP catalytic activity is essential for COPI vesicle formation, contrary to the hypothesis that it inhibits this process.
Conclusions:
- GAP plays a central role in coordinating cargo sorting and COPI vesicle formation.
- These findings necessitate a revised model for COPI transport mechanisms.
- Understanding GAP's function provides new insights into Golgi trafficking regulation.