title: GEF-effector interactions.
abstract: Members of the Arf family of small GTP-binding proteins, or GTPases, are activated by guanine nucleotide exchange factors (GEFs) that catalyze GDP release from their substrate Arf, allowing GTP to bind. In the secretory pathway, Arf1 is first activated by GBF1 at thecis-Golgi, then by BIG1 and BIG2 at thetrans-Golgi andtrans-Golgi network (TGN). Upon activation, Arf1-GTP interacts with effectors such as coat complexes, and is able to recruit different coat complexes to different membrane sites in cells. The COPI coat is primarily recruited tocis-Golgi membranes, whereas other coats, such as AP-1/clathrin, and GGA/clathrin, are recruited to thetrans-Golgi and the TGN. Although Arf1-GTP is required for stable association of these various coats to membranes, and is sufficientin vitro, other molecules, such as vesicle cargo and coat receptors on the membrane, contribute to specificity of coat recruitment in cells. Another mechanism to achieve specificity is interaction of effectors such as coats with the GEF itself, which would increase the concentration of a given coat in proximity to the site where Arf is activated, thus favoring its recruitment. This interaction between a GEF and an effector could also provide a mechanism for spatial organization of vesicle budding sites, similar to that described for Cdc42-mediated establishment of polarity sites such as the emerging bud in yeast. Another factor affecting the amount of freely diffusible Arf1-GTP in membranes is the GEF(s) themselves acting as effectors. Sec7p, the yeast homolog of mammalian BIG1 and BIG2, and Arno/cytohesin 2, a PM-localized Arf1 GEF, both bind to Arf1-GTP. This binding to the products of the exchange reaction establishes a positive feedback loop for activation.
authors.affiliation: Institut Jacques Monod, CNRS; Université Paris Diderot; Sorbonne Paris Cité ; Paris, France.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Jackson
keywords: ADP-ribosylation factor (Arf); Cdc42; Golgi Brefeldin A resistant guanine nucleotide exchange Factor 1 (GBF1); Guanine nucleotide exchange factor (GEF); Sec7; Turing-type mechanism; vesicle budding