GAT Domain Research Articles

The GGAs Promote ARF-Dependent Recruitment of Clathrin to the TGN

The GGAs constitute a family of modular adaptor-related proteins that bind ADP-ribosylation factors (ARFs) and localize to the trans-Golgi network (TGN) via their GAT domains. Here, we show that binding of the GAT domain stabilizes membrane-bound ARF1·GTP due to interference with the action of GTPase-activating proteins. We also show that the hinge and ear domains of the GGAs interact with clathrin in vitro, and that the GGAs promote recruitment of clathrin to liposomes in vitro and to TGN membranes in vivo. These observations suggest that the GGAs could function to link clathrin to membrane-bound ARF·GTP.

Sorting and Membrane Traffic

CELL BIOLOGY Soluble and membrane proteins destined for lysosomes or vacuoles are sorted from other proteins in the trans Golgi network (TGN). Three groups—Hirst et al. , Dell'Angelica et al. , and Boman et al. —have isolated proteins (named GGAs) that are involved in this process, most likely in the formation of coats on transport vesicles. The GGA proteins are structurally related to another class of coat proteins, the γ-adaptins, which are involved in trafficking proteins from the TGN to the plasma membrane. Immunoelectron microscopy and immunofluorescence microscopy localized the GGA proteins to the TGN. These proteins also contain a VHS domain, thought to be involved in membrane traffic and signal transduction, and a GAT domain that appears to be involved in targeting the GGA protein to the TGN membrane and in binding ARF1, a small GTP-binding protein already implicated in membrane traffic. In yeast strains lacking the GGA proteins vacuolar targeting of a hydrolase was defective. The identification of other coat proteins that interact with the GGAs should lead to a better understanding of the sorting machinery at the exit of the Golgi.— SMH J. Cell Biol. 149 , 67 (2000); J. Cell Biol. 149 , 81 (2000); Mol. Biol. Cell 11 , 1241 (2000).