Lo I-Chung, Gupta Vijay, Midde Krishna K, Taupin Vanessa, Lopez-Sanchez Inmaculada, Kufareva Irina, Abagyan Ruben, Randazzo Paul A, Farquhar Marilyn G, Ghosh Pradipta
Departments of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Dev Cell. 2015 Apr 20;33(2):189-203. doi: 10.1016/j.devcel.2015.02.009. Epub 2015 Apr 9.
A long-held tenet of heterotrimeric G protein signal transduction is that it is triggered by G protein-coupled receptors (GPCRs) at the PM. Here, we demonstrate that Gi is activated in the Golgi by GIV/Girdin, a non-receptor guanine-nucleotide exchange factor (GEF). GIV-dependent activation of Gi at the Golgi maintains the finiteness of the cyclical activation of ADP-ribosylation factor 1 (Arf1), a fundamental step in vesicle traffic in all eukaryotes. Several interactions with other major components of Golgi trafficking-e.g., active Arf1, its regulator, ArfGAP2/3, and the adaptor protein β-COP-enable GIV to coordinately regulate Arf1 signaling. When the GIV-Gαi pathway is selectively inhibited, levels of GTP-bound Arf1 are elevated and protein transport along the secretory pathway is delayed. These findings define a paradigm in non-canonical G protein signaling at the Golgi, which places GIV-GEF at the crossroads between signals gated by the trimeric G proteins and the Arf family of monomeric GTPases.
异源三聚体G蛋白信号转导的一个长期信条是，它由质膜上的G蛋白偶联受体（GPCR）触发。在这里，我们证明GIV/Girdin（一种非受体鸟嘌呤核苷酸交换因子（GEF））在高尔基体中激活Gi。GIV在高尔基体上对Gi的依赖性激活维持了ADP核糖基化因子1（Arf1）循环激活的有限性，这是所有真核生物囊泡运输中的一个基本步骤。与高尔基体运输的其他主要成分（如活性Arf1、其调节剂ArfGAP2/3和衔接蛋白β-COP）的几种相互作用使GIV能够协调调节Arf1信号传导。当GIV-Gαi途径被选择性抑制时，结合GTP的Arf1水平升高，沿分泌途径的蛋白质运输延迟。这些发现定义了高尔基体中非经典G蛋白信号传导的一个范例，该范例将GIV-GEF置于三聚体G蛋白门控信号和单体GTP酶的Arf家族之间的交叉点上。
