Golgicide A reveals essential roles for GBF1 in Golgi assembly and function

被引：183
作者：
Saenz, Jose B. [1 ,2 ]
Sun, William J. [1 ,2 ]
Chang, Jae Won [3 ,4 ]
Li, Jinmei [1 ,2 ]
Bursulaya, Badry [5 ]
Gray, Nathanael S. [3 ,4 ]
Haslam, David B. [1 ,2 ]
机构：
[1] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[3] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[5] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA
来源：
NATURE CHEMICAL BIOLOGY | 2009年 / 5卷 / 03期
关键词：
NUCLEOTIDE EXCHANGE FACTOR; BREFELDIN-A; TRANS-GOLGI; ENDOPLASMIC-RETICULUM; MEMBRANE-TRANSPORT; TYROSYLPROTEIN SULFOTRANSFERASE; RETROGRADE TRANSPORT; PLASMA-MEMBRANE; PROTEIN COMPLEX; SEC7; DOMAINS;
D O I：
10.1038/nchembio.144
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
ADP ribosylation factor 1 (Arf1) plays a critical role in regulating secretory traffic and membrane transport within the Golgi of eukaryotic cells. Arf1 is activated by guanine nucleotide exchange factors (ArfGEFs), which confer spatial and temporal specificity to vesicular transport. We describe here the discovery and characterization of golgicide A, a potent, highly specific, reversible inhibitor of the cis-Golgi ArfGEF GBF1. Inhibition of GBF1 function resulted in rapid dissociation of COPI vesicle coat from Golgi membranes and subsequent disassembly of the Golgi and trans-Golgi network. Secretion of soluble and membrane-associated proteins was arrested at the endoplasmic reticulum-Golgi intermediate compartment, whereas endocytosis and recycling of transferrin were unaffected by GBF1 inhibition. Internalized shiga toxin was arrested within the endocytic compartment and was unable to reach the dispersed trans-Golgi network. Collectively, these results highlight the central role for GBF1 in coordinating bidirectional transport and maintaining structural integrity of the Golgi.
引用
收藏
页码：157 / 165
页数：9
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