title: Arf activation at the Golgi is modulated by feed-forward stimulation of the exchange factor GBF1.
abstract: ADP-ribosylation factors (Arfs) play central roles in the regulation of vesicular trafficking through the Golgi. Arfs are activated at the Golgi membrane by guanine-nucleotide-exchange factors (GEFs) that are recruited from cytosol. Here, we describe a novel mechanism for the regulation of recruitment and activity of the ArfGEF Golgi-specific BFA resistance factor 1 (GBF1). Conditions that alter the cellular Arf-GDP:Arf-GTP ratio result in GBF1 recruitment. This recruitment of GBF1 occurs selectively on cis-Golgi membranes in direct response to increased Arf-GDP. GBF1 recruitment requires Arf-GDP myristoylation-dependent interactions suggesting regulation of a membrane-bound factor. Once recruited, GBF1 causes increased Arf-GTP production at the Golgi, consistent with a feed-forward self-limiting mechanism of Arf activation. This mechanism is proposed to maintain steady-state levels of Arf-GTP at the cis-Golgi during cycles of Arf-dependent trafficking events.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Douglas
authors.initials: D
authors.lastname: Quilty
authors.forename: Fraser
authors.initials: F
authors.lastname: Gray
authors.forename: Nathan
authors.initials: N
authors.lastname: Summerfeldt
authors.forename: Dan
authors.initials: D
authors.lastname: Cassel
authors.forename: Paul
authors.initials: P
authors.lastname: Melançon
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D055162:Biocatalysis; D016764:Cell Polarity; D025461:Feedback, Physiological; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008954:Models, Biological; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: C120445:GBF1 protein, human; D020662:Guanine Nucleotide Exchange Factors; D018129:Phosphatidylinositol Phosphates; D020033:Protein Isoforms; C037178:phosphatidylinositol 4-phosphate; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020727:ADP-Ribosylation Factors
keywords: Arf; Brefeldin A; GBF1; GTPase; Golgi