ArfGAPs; Depletion or Overexpression?

Abstract

Arf proteins are small GTP binding proteins that regulate intracellular traffic, actin remodeling and lipid metabolism. In the GTP-bound state, Arf is thought to be an active form that can bind to organelle membranes and many effectors. Arf in the GDP-bound state is thought to be an inactive form and released to cytosol. Arf GTPase Activating Proteins (ArfGAPs) hydrolyze Arf•GTP to Arf·GTP. Because GAPs "inactivate" small GTPases, the research of GAPs has often been done by overexpression of the GAPs looking at the biological consequences of the overexpression. However, decades of study about ArfGAP1 in COPI coated vesicle formation has led to a molecular model by which ArfGAP1 plays a role in fidelity of cargo sorting. This model implies that a deletion experiment would be appropriate to analyze the function of ArfGAP family proteins, rather than overexpression. Here, I briefly describe the role of ArfGAP1 in COPI coated vesicle formation, and discuss the biological consequences of depletion of ArfGAPs.