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LG186: an inhibitor of GBF1 function that causes Golgi disassembly in human and canine cells

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Boal, Frederic, Guetzoyan, Lucie, Sessions, Richard B., Zeghouf, Mahel, Spooner, Robert A. , Lord, Mike (J. Mike), Cherfils, Jacqueline, Clarkson, Guy J., Roberts, Lynne M. and Stephens, David J.. (2010) LG186: an inhibitor of GBF1 function that causes Golgi disassembly in human and canine cells. Traffic, Vol.11 (No.12). pp. 1537-1551. ISSN 1398-9219

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Official URL: http://dx.doi.org/10.1111/j.1600-0854.2010.01122.x

Abstract

Brefeldin A-mediated inhibition of ADP ribosylation factor (Arf) GTPases and their guanine nucleotide exchange factors, Arf-GEFs, has been a cornerstone of membrane trafficking research for many years. Brefeldin A (BFA) is relatively non-selective inhibiting at least three targets in human cells, Golgi brefeldin A resistance factor 1 (GBF1), brefeldin A inhibited guanine nucleotide exchange factor 1 (BIG1) and brefeldin A inhibited guanine nucleotide exchange factor 2 (BIG2). Here, we show that the previously described compound Exo2 acts through inhibition of Arf-GEF function, but causes other phenotypic changes that are not GBF1 related. We describe the engineering of Exo2 to produce LG186, a more selective, reversible inhibitor of Arf-GEF function. Using multiple-cell-based assays and GBF1 mutants, our data are most consistent with LG186 acting by selective inhibition of GBF1. Unlike other Arf-GEF and reported GBF1 inhibitors including BFA, Exo2 and Golgicide A, LG186 induces disassembly of the Golgi stack in both human and canine cells.

Item Type:

Journal Article

Subjects:

Q Science > QH Natural history > QH301 Biology

Divisions:

Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Faculty of Science > Chemistry

Journal or Publication Title:

Traffic

Publisher:

Wiley-Blackwell Publishing Ltd.

ISSN:

1398-9219