Golgicide A Reveals Essential Roles for GBF1 in Golgi Assembly and Function
Saenz, Jose B.
Sun, William J.
Chang, Jae Won
Haslam, David B.
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CitationSaenz, Jose B., William J. Sun, Jae Won Chang, Jinmei Li, Badry Bursulaya, Nathanael S. Gray, and David B. Haslam. 2012. Golgicide A reveals essential roles for GBF1 in golgi assembly and function. Nature Chemical Biology 5(3): 157-165.
AbstractADP-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 (GCA), a potent, highly specific, and 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 (TGN). Secretion of soluble and membrane-associated proteins was arrested at the ER-Golgi intermediate compartment, whereas endocytosis and recycling of transferrin was unaffected by GBF1 inhibition. Internalized shiga toxin was arrested within the endocytic compartment and was unable to reach the dispersed TGN. Collectively, these results highlight the central role for GBF1 in coordinating bidirectional transport and maintaining structural integrity of the Golgi.
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