LG186: An inhibitor of GBF1 function that causes Golgi disassembly in human and canine cells.
Traffic
; 11(12): 1537-51, 2010 Dec.
Article
in En
| MEDLINE
| ID: mdl-20854417
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Guanine Nucleotide Exchange Factors
/
Golgi Apparatus
/
Heterocyclic Compounds, 3-Ring
/
Hydrazones
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Traffic
Journal subject:
FISIOLOGIA
Year:
2010
Document type:
Article
Affiliation country:
Reino Unido