Nucleotide exchange on ARF mediated by yeast Gea1 protein

THE ADP-ribosylation factor ARF is a small GTP-binding protein that is involved in the transport of vesicles between the endoplasmic reticulum (ER) and Golgi complex and within the Golgi complex itself(1-4), ARF cycles between inactive and membrane-associated active forms as a result of exchange of bound GDP for GTP; the GTP-bound form is an essential participant in the formation of transport vesicles(4). This nucleotide exchange is inhibited by the fungal metabolite brefeldin A (BFA)(5,6), Here we identify a protein (Gea1) from Saccharomyces cerevisiae that is a component of a complex possessing guanine-nucleotide-exchange activity for ARF: We show that the activity of the complex is sensitive to brefeldin A and that Gea1 function is necessary for ER-Golgi transport in vivo, Gea1 contains a domain that is similar to a domain of Sec7, a protein necessary for intra-Golgi transport. We propose that Gea1 and ARNO, a human protein with a homologous Sed domain(7), are members of a new family of ARF guanine-nucleotide exchange factors.