A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome

We have cloned and characterized members of a novel family of proteins, the GGAs. These proteins contain an NH2-terminal VHS domain, one or two coiled -coil domains, and a COOH-terminal domain homologous to the COOH-terminal " ear" domain of gamma-adaptin. However, unlike gamma-adaptin, the GGAs are n ot associated with clathrin-coated vesicles or with any of the components o f the AP-1 complex. GGA1 and GGA2 are also not associated with each other, although they colocalize on perinuclear membranes. Immunogold EM shows that these membranes correspond to trans elements of the Golgi stack and the TG N. GST pulldown experiments indicate that the GGA COOH-terminal domains bin d to a subset of the proteins that bind to the gamma-adaptin COOH-terminal domain. In yeast there are two GGA genes. Deleting both of these genes resu lts in missorting of the vacuolar enzyme carboxypeptidase Y, and the cells also have a defective vacuolar morphology phenotype. These results indicate that the function of the GGAs is to facilitate the trafficking of proteins between the TGN and the vacuole. or its mammalian equivalent, the lysosome .