Department of Cell Biology, Faculty of Biology, University of Seville, 41012 Seville, Spain.
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Seville, Spain.
Int J Mol Sci. 2021 Jan 3;22(1):423. doi: 10.3390/ijms22010423.
Golgi trafficking depends on the small GTPase Arf1 which, upon activation, drives the assembly of different coats onto budding vesicles. Two related types of guanine nucleotide exchange factors (GEFs) activate Arf1 at different Golgi sites. In yeast, Gea1 in the -Golgi and Gea2 in the medial-Golgi activate Arf1 to form COPI-coated vesicles for retrograde cargo sorting, whereas Sec7 generates clathrin/adaptor-coated vesicles at the -Golgi network (TGN) for forward cargo transport. A central question is how the same activated Arf1 protein manages to assemble different coats depending on the donor Golgi compartment. A previous study has postulated that the interaction between Gea1 and COPI would channel Arf1 activation for COPI vesicle budding. Here, we found that the p24 complex, a major COPI vesicle cargo, promotes the binding of Gea1 with COPI by increasing the COPI association to the membrane independently of Arf1 activation. Furthermore, the p24 complex also facilitates the interaction of Arf1 with its COPI effector. Therefore, our study supports a mechanism by which the p24 complex contributes to program Arf1 activation by Gea1 for selective COPI coat assembly at the -Golgi compartment.
高尔基体内运输依赖于小分子 GTP 酶 Arf1,其被激活后可驱动不同包被蛋白在出芽小泡上的组装。两种相关类型的鸟嘌呤核苷酸交换因子(GEFs)在高尔基体的不同部位激活 Arf1。在酵母中,-高尔基体中的 Gea1 和中间高尔基体中的 Gea2 激活 Arf1 以形成 COPI 包被小泡,用于逆行货物分拣,而 Sec7 在 -高尔基体网络(TGN)生成网格蛋白/衔接蛋白包被小泡,用于正向货物运输。一个核心问题是,相同的激活的 Arf1 蛋白如何根据供体高尔基体隔室组装不同的包被。先前的研究假设 Gea1 和 COPI 之间的相互作用将引导 Arf1 激活以形成 COPI 小泡。在这里,我们发现 p24 复合物,一种主要的 COPI 小泡货物,通过增加 COPI 与膜的结合,独立于 Arf1 激活,促进 Gea1 与 COPI 的结合。此外,p24 复合物还促进了 Arf1 与其 COPI 效应物的相互作用。因此,我们的研究支持了一种机制,即 p24 复合物通过 Gea1 为选择性 COPI 包被在 -高尔基体隔室中的组装贡献了 Arf1 激活程序。