ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation.
Examining how key components of coat protein I (COPI) transport participate in cargo sorting, we find that, instead of ADP ribosylation factor 1 (ARF1), its GTPase-activating protein (GAP) plays a direct role in promoting the binding of cargo proteins by coatomer (the core COPI complex). Activated ARF1 binds selectively to SNARE cargo proteins, with this binding likely to represent at least a mechanism by which activated ARF1 is stabilized on Golgi membrane to propagate its effector functions. We also find that the GAP catalytic activity plays a critical role in the formation of COPI vesicles from Golgi membrane, in contrast to the prevailing view that this activity antagonizes vesicle formation. Together, these findings indicate that GAP plays a central role in coupling cargo sorting and vesicle formation, with implications for simplifying models to describe how these two processes are coupled during COPI transport.
Lee
Stella Y
SY
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA 02115.
Yang
Jia-Shu
JS
Hong
Wanjin
W
Premont
Richard T
RT
Hsu
Victor W
VW
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D022181:COP-Coated Vesicles / Q000378:metabolism*; D020755:Coat Protein Complex I / Q000378:metabolism / Q000502:physiology*; D020756:Coatomer Protein / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins; D022161:Transport Vesicles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
D020755:Coat Protein Complex I; D020756:Coatomer Protein; D020690:GTPase-Activating Proteins; D011994:Recombinant Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D006160:Guanosine Triphosphate; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors