Quilty Douglas, Gray Fraser, Summerfeldt Nathan, Cassel Dan, Melançon Paul
Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
J Cell Sci. 2014 Jan 15;127(Pt 2):354-64. doi: 10.1242/jcs.130591. Epub 2013 Nov 8.
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.
ADP-核糖基化因子（Arfs）在通过高尔基体的囊泡运输调节中发挥核心作用。Arfs在高尔基体膜上被从胞质溶胶募集而来的鸟嘌呤核苷酸交换因子（GEFs）激活。在此，我们描述了一种调节Arf鸟嘌呤核苷酸交换因子高尔基体特异性BFA抗性因子1（GBF1）募集和活性的新机制。改变细胞中Arf-GDP:Arf-GTP比例的条件会导致GBF1的募集。GBF1的这种募集直接响应于Arf-GDP的增加，选择性地发生在顺式高尔基体膜上。GBF1的募集需要Arf-GDP肉豆蔻酰化依赖性相互作用，提示对一种膜结合因子的调节。一旦被募集，GBF1会导致高尔基体处Arf-GTP产生增加，这与Arf激活的前馈自限机制一致。该机制被认为在Arf依赖性运输事件的循环过程中维持顺式高尔基体处Arf-GTP的稳态水平。
