Differential Roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI Trafficking

J Cell Biol. 2008 Nov 17;183(4):725-35. doi: 10.1083/jcb.200806140.

Abstract

The formation of coat protein complex I (COPI)-coated vesicles is regulated by the small guanosine triphosphatase (GTPase) adenosine diphosphate ribosylation factor 1 (Arf1), which in its GTP-bound form recruits coatomer to the Golgi membrane. Arf GTPase-activating protein (GAP) catalyzed GTP hydrolysis in Arf1 triggers uncoating and is required for uptake of cargo molecules into vesicles. Three mammalian ArfGAPs are involved in COPI vesicle trafficking; however, their individual functions remain obscure. ArfGAP1 binds to membranes depending on their curvature. In this study, we show that ArfGAP2 and ArfGAP3 do not bind directly to membranes but are recruited via interactions with coatomer. In the presence of coatomer, ArfGAP2 and ArfGAP3 activities are comparable with or even higher than ArfGAP1 activity. Although previously speculated, our results now demonstrate a function for coatomer in ArfGAP-catalyzed GTP hydrolysis by Arf1. We suggest that ArfGAP2 and ArfGAP3 are coat protein-dependent ArfGAPs, whereas ArfGAP1 has a more general function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Animals
  • Cell Line
  • Coat Protein Complex I / genetics
  • Coat Protein Complex I / metabolism*
  • Coated Vesicles / genetics
  • Coated Vesicles / metabolism*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism
  • Humans
  • Protein Transport / physiology
  • Rats

Substances

  • ARFGAP1 protein, human
  • ARFGAP3 protein, human
  • Arfgap1 protein, rat
  • Coat Protein Complex I
  • GTPase-Activating Proteins
  • ADP-Ribosylation Factor 1
  • ADP-Ribosylation Factors
  • ARFGAP2 protein, human