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.
Feng
Yan
Y
Institute of Chemistry and Cell Biology, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. yfeng@hms.harvard.edu
Yu
Sidney
S
Lasell
Troy K R
TK
Jadhav
Ashutosh P
AP
Macia
Eric
E
Chardin
Pierre
P
Melancon
Paul
P
Roth
Michael
M
Mitchison
Timothy
T
Kirchhausen
Tomas
T
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