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. 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. This nucleotide exchange is inhibited by the fungal metabolite brefeldin A (BFA). 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 Sec7 domain, are members of a new family of ARF guanine-nucleotide exchange factors.
Peyroche
A
A
Service de Biochimie et Génétique Moléculaire, Département de Biologie Cellulaire et Moléculaire, CEA/Saclay, Gif-sur-Yvette, France.
Paris
S
S
Jackson
C L
CL
D020727:ADP-Ribosylation Factors; D001692:Biological Transport / Q000235:genetics; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; C102475:GEA1 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors