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Golgicide A Reveals Essential Roles for GBF1 in Golgi Assembly and Function

Golgicide A Reveals Essential Roles for GBF1 in Golgi Assembly and Function

José B Sáenz, William J Sun, Jae Won Chang, Jinmei Li, Badry Bursulaya, Nathanael S Gray, David B Haslam

Nat Chem Biol. 2009 Mar;5(3):157-65.

PMID: 19182783

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1005036736	Golgicide A		1005036-73-6	Price

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