Exo1: a new chemical inhibitor of the exocytic pathway.
A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation.
Institute of Chemistry and Cell Biology, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. yfeng@hms.harvard.edu
Yan
Y
Feng
Sidney
S
Yu
Troy K R
TK
Lasell
Ashutosh P
AP
Jadhav
Eric
E
Macia
Pierre
P
Chardin
Paul
P
Melancon
Michael
M
Roth
Timothy
T
Mitchison
Tomas
T
Kirchhausen
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010641:Phenotype
C568977:2-(4-fluorobenzoylamino)benzoic acid methyl ester; D001549:Benzamides; D001565:Benzoates; D020662:Guanine Nucleotide Exchange Factors; D020126:Brefeldin A; D000246:Adenosine Diphosphate Ribose