ADP-ribosylation factor/COPI-dependent events at the endoplasmic reticulum-Golgi interface are regulated by the guanine nucleotide exchange factor GBF1
ADP-ribosylation factor/COPI-dependent events at the endoplasmic reticulum-Golgi interface are regulated by the guanine nucleotide exchange factor GBF1
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DOI：
10.1091/mbc.e02-11-0730
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发表时间：
2003-06-01
影响因子：
3.3
通讯作者：
Elizabeth, S
中科院分区：
文献类型：
--
作者：
García-Mata, R;Szul, T;Elizabeth, S
adp -核糖基化因子（ARF）介导的COPI向膜的募集在内质网之间的运输中起着核心作用。（ER）和高尔基体arf的激活是由鸟嘌呤核苷酸交换因子介导的。虽然已经确定了几个arf - gef，但对它们发挥作用的运输步骤仍然知之甚少。本文作者报道了gef的sec7结构域家族成员GBF1负责调控er -高尔基界面上copi介导的事件。研究表明，GBF1对前高尔基体的形成、分化和易位以及维持高尔基体完整性至关重要。我们还表明，转运能力强的er -to-高尔基体的形成分两个阶段进行：首先，与copi无关的事件导致不稳定隔室的形成，该隔室在缺乏GBF1活性的情况下被迅速重吸收。其次，GBF1与该隔室的关联允许COPI招募并导致其成熟为运输中间体。我们的研究结果表明，在膜运输和高尔基生物发生的基础上，持续的膜重构需要GBF1向空间分化膜结构域的持续募集。
ADP-ribosylation factor (ARF) mediated recruitment of COPI to membranes plays a central role in transport between the endoplasmic reticulum. (ER) and the Golgi. The activation of ARFs is mediated by guanine nucleotide exchange factors (GEFs). Although several ARF-GEFs have been identified, the transport steps in which they function are still poorly understood. Here we report that GBF1, a member of the Sec7-domain family of GEFs, is responsible for the regulation of COPI-mediated events at the ER-Golgi interface. We show that GBF1 is essential for the formation, differentiation, and translocation of pre-Golgi intermediates and for the maintenance of Golgi integrity. We also show that the formation of transport-competent ER-to-Golgi intermediates proceeds in two stages: first, a COPI-independent event leads to the formation of an unstable compartment, which is rapidly reabsorbed in the absence of GBF1 activity. Second, the association of GBF1 with this compartment allows COPI recruitment and leads to its maturation into transport intermediates. The recruitment of GBF1 to this compartment is specifically inhibited by brefeldin A. Our findings imply that the continuous recruitment of GBF1 to spatially differentiated membrane domains is required for sustained membrane remodeling that underlies membrane traffic and Golgi biogenesis.