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Published 14 October 2002. doi:10.1083/jcb1591iti5
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© The Rockefeller University Press, 0021-9525/2002/10/13-b $5.00
The Journal of Cell Biology, Volume 159, Number 1, 13-b-13


In This Issue

A GAP in COPI vesicle formation is filled


Without ARFGAP1 or GTP, vesicles cannot load their cargo.

The effect of ARF1 GTPase-activating protein (ARFGAP1) on vesicle formation is making a turn-around. Contrary to previous theories, GAP does not antagonize COPI coat recruitment. As shown by Yang et al. on page 69, its newly discovered function reveals conservation among GAPs in anterograde and retrograde transport pathways.

COPI vesicle formation is initiated by the ADP-Ribosylation Factor (ARF) family of small GTPases, which recruits COPI coatomer subunits to Golgi membranes. ARFGAP1 inactivates ARF1 by stimulating GTP hydrolysis. Because COPI vesicles formed in vitro using nonhydrolyzable GTP (GTP{gamma}S) or GTP-bound ARF1 do not uncoat, it has been inferred that ARFGAP1 stimulates uncoating, and thus inhibits vesicle formation. But the new experiments, using hydrolyzable GTP, provide a clearer view of the ARFGAP1 function.

Yang et al. found that ARFGAP1 had the opposite effect of what was previously thought—it stimulated vesicle formation. ARFGAP1 was required for cargo sorting and was found on vesicles at levels exceeding even that of COPI. Thus, ARFGAP1 is actually a COPI coat component, similar to the GAP Sec23p on COPII vesicles. In the COPI case, GTP was required for ARF1 to bring ARFGAP1 to the site of vesicle formation. GTP{gamma}S blocked this recruitment, and thus blocked vesicle formation altogether. Additional shearing manipulations in previous in vitro experiments may have masked the requirement for ARFGAP1 in vesicle formation by releasing abnormal vesicles. {blacksquare}



Nicole LeBrasseur

lebrasn{at}rockefeller.edu


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Related Article

ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat
Jia-Shu Yang, Stella Y. Lee, Minggeng Gao, Sylvain Bourgoin, Paul A. Randazzo, Richard T. Premont, and Victor W. Hsu
J. Cell Biol. 2002 159: 69-78. [Abstract] [Full Text] [PDF]




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