4.8 Article

Exo1: A new chemical inhibitor of the exocytic pathway

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0631766100

Keywords

Golgi; ADP-ribosylation factor; endoplasmic reticulum (ER); imaging-based screen; Bars50

Funding

  1. NIGMS NIH HHS [R01 GM36548-17, P01 GM062566, P01 GM62566-02, R01 GM036548] Funding Source: Medline

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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 (ARIF) 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.

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